Charcot arthropathy is a progressive condition of the musculoskeletal system that is characterized by joint dislocations, pathologic fractures, and debilitating deformities. It results in progressive destruction of bone and soft tissues at weight-bearing joints. In its most severe form, it may cause significant disruption of the bony architecture.
Charcot arthropathy can occur at any joint; however, it occurs most commonly in the lower extremity, at the foot and ankle. Diabetes is now considered to be the most common aetiology of Charcot arthropathy.

The patient has hyperinsulinemia and hypoglycaemia, but her C-peptide levels are normal. This is strongly suggestive of the fact that she is self-administering insulin.
In Insulinoma, common diagnostic criteria include:
– blood glucose level < 50 mg/dl with hypoglycaemic symptoms,
– relief of symptoms after eating
– absence of sulfonylurea on plasma assays.
The classic diagnostic criteria include the demonstration of the following during a supervised fast:
Increased plasma insulin level
Increased C peptide level
Increased proinsulin level
However, the patient has normal C-peptide levels.
In type-1 diabetes mellitus, insulin and C-peptide levels are low.

In central and nephrogenic diabetes insipidus (DI), urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI.

In primary polydipsia, water deprivation results in an increase in urine osmolality, anywhere between 300 – 800 mOsm/Kg (usually up to 600 – 700 mOsm/Kg), without a substantial increase in plasma osmolality, but the increase in urine osmolality is not as substantial as in a normal response.

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon. GLP-1 is released in response to meal intake.
The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the ileal brake mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake.
Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycaemia.

Sitagliptin-induced pancreatitis can occur at any time after the initiation of therapy, even after several years. Patients taking sitagliptin who present with signs and symptoms of mild or severe pancreatitis should immediately discontinue sitagliptin and use an alternate medication regimen for control of type 2 diabetes.
In response to pancreatitis reported in post-marketing surveillance through the Adverse Event Reporting System (AERS), the FDA has issued revised prescribing information for sitagliptin stating that cases of acute pancreatitis have been reported with use, to monitor closely for signs and symptoms of pancreatitis, and to use sitagliptin with caution in patients with a history of pancreatitis.

Acromegaly occurs due to excessive action of insulin-like growth factor I (IGF-I) after the growth plate cartilage fuses in adulthood.
It can be an insidious disease. Symptoms, which may precede diagnosis by several years, can be divided into the following groups:
1. Symptoms due to local mass effects of an intracranial tumour
Tumour damage to the pituitary stalk may cause hyperprolactinemia (Increased blood prolactin levels associated with galactorrhoea) due to loss of inhibitory regulation of prolactin secretion by the hypothalamus
2. Symptoms due to excess of GH/IGF-I including:
– Hyperhidrosis (Not hypohidrosis)
– Arthritis
– Peripheral Neuropathies e.g. Carpal Tunnel Syndrome

The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunologic functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T cells.
DiGeorge’s syndrome (DGS) is a developmental abnormality affecting the thymus. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcaemia (resulting from parathyroid hypoplasia).

Dapagliflozin works by inhibiting sodium glucose cotransporter 2 (SGLT2) and blocking resorption of glucose in the kidney, leading to an increase in urinary glucose excretion and lowering of both plasma glucose levels and body weight.
All studies with SGLT2 inhibitors have found significant reductions in BP, with greater reductions seen in systolic (1.66 to 6.9mmHg) than diastolic (0.88 to 3.5mmHg) BP.
While some trials have shown no change in lipid parameters, others have shown a modest but statistically significant increase in both HDL and LDL cholesterol with no effect on triglycerides or the LDL/HDL ratio.

Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations.
Evidence from studies is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:
1. Induction of lipoprotein lipolysis.
2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production.
3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which is thus catabolized more rapidly.
4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.
5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in the liver, which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Approximately 95% of patients with type 1 DM have either HLA-DR3 or HLA-DR4. Although the genetic aspect of type 1 DM is complex, with multiple genes involved, there is a high sibling relative risk. Whereas dizygotic twins have a 5-6% concordance rate for type 1 DM, monozygotic twins will share this diagnosis more than 50% of the time by the age of 40 years.

Oestrogen therapy reduces plasma levels of LDL cholesterol and increases levels of HDL cholesterol. It can improve endothelial vascular function, however, it also has adverse physiological effects, including increasing the plasma levels of triglycerides (small dense LDL particles). Therefore, although HRT may have direct beneficial effects on cardiovascular outcomes, these effects may be reduced or balanced by the adverse physiological effects.

Primary hyperparathyroidism (PHPT) is diagnosed based upon levels of blood calcium and parathyroid hormone (PTH). In most people with PHPT, both levels are higher than normal. Occasionally, a person may have an elevated calcium level and a normal or minimally elevated PTH level. Since PTH should normally be low when calcium is elevated, a minimally elevated PTH is considered abnormal and indicates PHPT.

Insulin is produced by the beta-cells in the islets of Langerhans in the pancreas while Glucagon is secreted from the alpha cells of the pancreatic islets of Langerhans.
Type 1 diabetes mellitus is the culmination of lymphocytic infiltration and destruction of the beta cells of the islets of Langerhans in the pancreas. As beta-cell mass declines, insulin secretion decreases until the available insulin is no longer adequate to maintain normal blood glucose levels. After 80-90% of the beta cells are destroyed, hyperglycaemia develops and diabetes may be diagnosed.

A fasting blood glucose level from 110 to 126 mg/dL (5.5 to 6.9 mmol/L) is considered prediabetes. This result is sometimes called impaired fasting glucose.
Diabetes mellitus (type 2): diagnosis

The diagnosis of type 2 diabetes mellitus can be made by plasma glucose. If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

The patient has Cushing syndrome suggested by the elevated 24hr urine free cortisol. Hence, the mass is most probably a cortisol secreting adenoma.

The clinical manifestations of Small cell lung cancer (SCLC) can result from local tumour growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.
Hypertrophic pulmonary osteoarthropathy (HPO) is a rare paraneoplastic syndrome that is frequently associated with lung cancer; however, the incidence of clinically apparent HPO is not well known.
SIADH is present in 15% of cases and most commonly seen.
Although hypercalcaemia is frequently associated with malignancy, it is very rare in small cell lung cancer despite the high incidence of lytic bone metastases.
Ectopic Cushing’s syndrome in SCLC does not usually exhibit the classic signs of Cushing’s syndrome and Cushing’s syndrome could also appear during effective chemotherapy.
Chemotherapy is the treatment of choice in SCLC.

Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum thyroiditis) in the 2-12 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes mellitus.

Some patients return spontaneously to a euthyroid state within a few months, but most patients experience a phase of hypothyroidism that takes 2 to 6 months to resolve; of this group, some develop permanent hypothyroidism. About 50% of patients, however, will develop permanent hypothyroidism within 5 years of the diagnosis of postpartum thyroiditis.

High titres of anti-TPO antibodies during pregnancy have been reported to have high sensitivity and specificity for postpartum autoimmune thyroid disease.

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:
Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP])
Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney.
The boy most probably has nephrogenic diabetes insidious (DI) not central DI so he is not responding to the ADH treatment.

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.
Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.

Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

This patient has hypercalcaemia due to hyperparathyroidism. However, the intestinal absorption of calcium is mainly controlled by 1,25 dihydroxy-vitamin D. Under the influence of calcitriol (active form of vitamin D), intestinal epithelial cells increase their synthesis of calbindin (calcium-binding carrier protein) necessary for active calcium ion absorption.

Carcinoid tumours are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. They can be seen in other organs, including the lungs, mediastinum, thymus, liver, bile ducts, pancreas, bronchus, ovaries, prostate, and kidneys. While carcinoid tumours tend to grow slowly, they have the potential to metastasise.
Signs and symptoms seen in larger tumours may include the following:
– Periodic abdominal pain: Most common presentation for a small intestinal carcinoid; often associated with malignant carcinoid syndrome.
– Cutaneous flushing: Early and frequent (94%) symptom; typically affects head and neck.
– Diarrhoea and malabsorption (84%): Watery, frothy, or bulky stools, gastrointestinal (GI) bleed or steatorrhea; may or may not be associated with abdominal pain, flushing, and cramps.
– Cardiac manifestations (60%): Valvular heart lesions, fibrosis of the endocardium; may lead to heart failure with tachycardia and hypertension.
– Wheezing or asthma-like syndrome (25%): Due to bronchial constriction; some tremors are relatively indolent and result in chronic symptoms such as cough and dyspnoea.
– Pellagra with scale-like skin lesions, diarrhoea and mental disturbances.
– Carcinoid crisis can be the most serious symptom of the carcinoid tumours and life-threatening. It can occur suddenly or after stress, including chemotherapy and anaesthesia.

Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 is considered mild or subclinical hypothyroidism.
Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be asymptomatic. Symptoms and signs are often subtle and neither sensitive nor specific.
The following are symptoms of hypothyroidism:
– Fatigue, loss of energy, lethargy
– Weight gain
– Decreased appetite
– Cold intolerance
– Dry skin
– Hair loss
– Sleepiness
– Muscle pain, joint pain, weakness in the extremities
– Depression
– Emotional lability, mental impairment
– Forgetfulness, impaired memory, inability to concentrate
– Constipation
– Menstrual disturbances, impaired fertility
– Decreased perspiration
– Paraesthesia and nerve entrapment syndromes
– Blurred vision
– Decreased hearing
– Fullness in the throat, hoarseness
Physical signs of hypothyroidism include the following:
– Weight gain
– Slowed speech and movements
– Dry skin
– Jaundice
– Pallor
– Coarse, brittle, straw-like hair
– Loss of scalp hair, axillary hair, pubic hair, or a combination
– Dull facial expression
– Coarse facial features
– Periorbital puffiness
– Macroglossia
– Goitre (simple or nodular)
– Hoarseness
– Decreased systolic blood pressure and increased diastolic blood pressure
– Bradycardia
– Pericardial effusion
– Abdominal distention, ascites (uncommon)
– Hypothermia (only in severe hypothyroid states)
– Nonpitting oedema (myxoedema)
– Pitting oedema of lower extremities
– Hyporeflexia with delayed relaxation, ataxia, or both.

Osteopenia is an early sign of bone weakening that is less severe than osteoporosis.
The numerical result of the bone density test is quantified as a T score. The lower the T score, the lower the bone density. T scores greater than -1.0 are considered normal and indicate healthy bone. T scores between -1.0 and -2.5 indicate osteopenia. T scores lower than -2.5 indicate osteoporosis.
DEXA also provides the patient’s Z-score, which reflects a value compared with that of person matched for age and sex.
Z-score values of –2.0 SD or lower are defined as below the expected range for age and those above –2.0 SD as within the expected range for age.

Once thyrotoxicosis has been identified by laboratory values, the thyroid radio-iodine uptake and scan may be used to help distinguish the underlying aetiology. Thyroid radioiodine uptake is raised in Graves’ disease. It may be normal or raised in patients with a toxic multinodular goitre. It is very low or undetectable in thyrotoxicosis resulting from exogenous administration of thyroid hormone or the thyrotoxic phase of thyroiditis.

The combination of Insulinoma and Parathyroid diseases is suggestive of MEN 1 syndrome.
Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumour syndrome inherited in an autosomal dominant manner and characterized by a predisposition to a multitude of endocrine neoplasms primarily of parathyroid, entero-pancreatic, and anterior pituitary origin, as well as non-endocrine neoplasms.
Other endocrine tumours in MEN1 include foregut carcinoid tumours, adrenocortical tumours, and rarely pheochromocytoma. Nonendocrine manifestations include meningiomas and ependymomas, lipomas, angiofibromas, collagenomas, and leiomyomas.

Primary hyperparathyroidism (PHPT), due to parathyroid hyperplasia is the most frequent and usually the earliest expression of MEN-1, with a typical age of onset at 20–25 years.

Bicarbonate therapy is not indicated in mild and moderate forms of DKA because metabolic acidosis will correct with insulin therapy. The use of bicarbonate in severe DKA is controversial due to a lack of prospective randomized studies. It is thought that the administration of bicarbonate may actually result in peripheral hypoxemia, worsening of hypokalaemia, paradoxical central nervous system acidosis, cerebral oedema in children and young adults, and an increase in intracellular acidosis. Because severe acidosis is associated with worse clinical outcomes and can lead to impairment in sensorium and deterioration of myocardial contractility, bicarbonate therapy may be indicated if the pH is 6.9 or less.

Cabergoline, an ergot derivative, is a long-acting dopamine agonist. It is usually better tolerated than Bromocriptine (BEC), and its efficacy profiles are somewhat superior to those of BEC. It offers the convenience of twice-a-week administration, with a usual starting dose of 0.25 mg biweekly to a maximum dose of 1 mg biweekly. Some studies have shown efficacy even with once-a-week dosing. Cabergoline appears to be more effective in lowering prolactin levels and restoring ovulation. Up to 70% of patients who do not respond to BEC respond to cabergoline.

Elderly patients with severe hypothyroidism often present with variable symptoms that may be masked or potentiated by co-morbid conditions. Characteristic symptoms may include fatigue, weight gain, cold intolerance, hoarseness, constipation, and myalgias. Neurologic symptoms may include ataxia, depression, and mental status changes ranging from mild confusion to overt dementia.
Clinical findings that may raise suspicion of thyroid hormone deficiency include hypothermia, bradycardia, goitrous enlargement of the thyroid, cool dry skin, myxoedema, delayed relaxation of deep tendon reflexes, a pericardial or abdominal effusion, hyponatremia, and hypercholesterolemia.

The patient has a greatly reduced free T4 concentration, is hypothermic, unconscious and has evidence of associated heart failure. All of those support the diagnosis of profound hypothyroidism.

Three classes of medications are appropriate for the management of major triglyceride elevations: fibric acid derivatives, niacin, and omega-3 fatty acids.

Fibrate is used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

High-dose niacin (vitamin B-3) (1500 or more mg/d) decreases triglyceride levels by at least 40% and can raise HDL cholesterol levels by 40% or more. Niacin also reliably and significantly lowers LDL cholesterol levels, which the other major triglyceride-lowering medications do not.

Omega-3 fatty acids are attractive because of their low risk of major adverse effects or interaction with other medications. At high doses (>4 g/d), triglycerides are reduced.

Patients with diabetes often develop ophthalmic complications, the most common and potentially most blinding of these complications is diabetic retinopathy.
The following are the 5 stages in the progression of diabetic retinopathy:
1. Dilation of the retinal venules and formation of retinal capillary microaneurysms.
2. Increased vascular permeability.
3. Vascular occlusion and retinal ischemia.
4. Proliferation of new blood vessels on the surface of the retina.
5. Vitreous haemorrhage and contraction of the fibrovascular proliferation.
The first 2 stages of diabetic retinopathy are known as background or nonproliferative retinopathy. Initially, the retinal venules dilate, then microaneurysms (tiny red dots on the retina that cause no visual impairment) appear. As the microaneurysms or retinal capillaries become more permeable, hard exudates appear, reflecting the leakage of plasma.

Mild nonproliferative diabetic retinopathy (NPDR) or background diabetic retinopathy is indicated by the presence of at least 1 microaneurysm, while neovascularization is the hallmark of Proliferative Diabetic Retinopathy (PDR).

Sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated.
Organic nitrates and nitric oxide (NO) donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO via increasing cGMP concentrations.

European guidelines for the treatment of syndrome of inappropriate antidiuresis include the following recommendations for the management of moderate or profound hyponatremia:
– Restrict fluid intake as first-line treatment.
– Second-line treatments include increasing solute intake with 0.25–0.50 g/kg per day or a combination of low-dose loop diuretics and oral sodium chloride.
– Use of lithium, demeclocycline, or vasopressin receptor antagonists is not recommended.
Recommendations on the treatment of SIADH from an American Expert Panel included the following:
– If chronic, limit the rate of correction.
– Fluid restriction should generally be first-line therapy.
– Consider pharmacologic therapies if serum Na + is not corrected after 24-48 hr of fluid restriction or if the patient has a low urinary electrolyte free water excretion.
– Patients being treated with vaptans should not be on a fluid restriction initially.
– Water, 5% dextrose or desmopressin can be used to slow the rate of correction if the water diuresis is profound.

Free T4 levels or the free T4 index is usually elevated, as is the free T3 level or free T3 index
– Assays for thyrotropin-receptor antibodies (particularly TSIs) almost always are positive.
– Detection of TSIs is diagnostic for Graves disease.
– Other markers of thyroid autoimmunity, such as antithyroglobulin antibodies or antithyroid peroxidase antibodies, are usually present.
– Other autoantibodies that may be present include thyrotropin receptor-blocking antibodies and anti–sodium-iodide symporter antibody.
The presence of these antibodies supports the diagnosis of autoimmune thyroid disease.
– The radioactive iodine uptake is increased and the uptake is diffusely distributed over the entire gland.

Exogenous thyroid hormone use has been associated with episodes of thyroid storm as well as thyrotoxic periodic paralysis.
It presents with marked proximal muscle weakness in both upper and lower limbs, hypokalaemia and signs of hyperthyroidism.
Hyperthyroidism generally presents with tachycardia, hypertension, hyperthermia, and cardiac arrhythmias

Laxatives and diuretics can result in electrolyte abnormalities.
Medical complications associated with laxatives include chronic diarrhoea which disrupts the normal stool electrolyte concentrations that then leads to serum electrolyte shifts; acutely, hypokalaemia is most typically seen. The large intestine suffers nerve damage from the chronic laxative use that renders it unable to function properly. The normal peristalsis and conduction are affected; the disorder is thought to be secondary to a degeneration of Auerbach’s Plexi. However, it does not cause muscle weakness.

Insulin tends to cause weight gain, not weight loss.
Metformin does not cause muscle weakness but can cause headaches.

Lactic acidosis is occasionally responsible for metabolic acidosis in diabetics. It may occur in the presence of normal blood levels of the ketone bodies, and such cases are often described as having “non-ketotic diabetic acidosis.
It is most commonly associated with tissue hypoperfusion and states of acute circulatory failure.
Appropriate measures include treatment of shock, restoration of circulating fluid volume, improved cardiac function, identification of sepsis source, early antimicrobial intervention, and resection of any potential ischemic regions. Reassessment of lactate levels for clearance assists ongoing medical management.

Indications for surgery for the treatment of primary hyperparathyroidism:
1. Symptoms of hypercalcaemia such as thirst, frequent or excessive urination, or constipation
2. End-organ disease (renal stones, fragility fractures or osteoporosis)
3. An albumin-adjusted serum calcium level of 2.85 mmol/litre or above.

The somatotroph cells of the anterior pituitary gland produce growth hormone (GH).
GH deficiency in adults usually manifests as reduced physical performance and impaired psychological well-being. It results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life.

The patients high morning blood sugar levels are suggestive to Somogyi Phenomenon which suggests that hypoglycaemia during the late evening induced by insulin could cause a counter regulatory hormone response that produces hyperglycaemia in the early morning.
Substitution of regular insulin with an immediate-acting insulin analogue, such as Humulin lispro, may be of some help.

It has been determined that HPV infection is the most powerful epidemic factor. This virus is needed, but not sufficient for the development of cervical cancer.
The WHO’s International Agency for Research on Cancer (IARC) classified HPV infection as carcinogenic to humans (HPV types 16 and 18), probably carcinogenic (HPV types 31 and 33) and possibly carcinogenic (other HPV types except 6 and 11).
Tobacco smoking, the use of contraceptives, and the number of births are factors that showed no statistically significant deviations in the studied population compared to other countries in the region, as well as European countries. They have an equal statistical significance in all age groups.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Biguanides (Metformin):
People who take metformin alone should be able to fast safely given that the possibility of hypoglycaemia is minimal. However, patients should modify its dose and administration timing to provide two-thirds of the total daily dose, which should be taken immediately with the sunset meal, while the other third is taken before the predawn meal.

Thiazolidinediones: No change needed.

Sulfonylurea:
Once-daily sulfonylurea (such as glimepiride or gliclazide MR): the total daily dose should be taken with the sunset meal.
Shorter-acting sulfonylurea (such as gliclazide twice daily): the same daily dose remains unchanged, and one dose should be taken at the sunset meal and the other at the predawn meal.
Long-acting sulfonylurea (such as glibenclamide): these agents should be avoided.

It is important that diabetic patients to eat a healthy balanced diet and choose foods with a low glycaemic index (such as complex carbohydrates), which can help to maintain blood glucose levels during fasting. Moreover, it is crucial to consume adequate fluids to prevent dehydration. Physical activity is encouraged, especially during non-fasting periods.

Autonomic Neuropathy may involve the cardiovascular, gastrointestinal, genitourinary systems and the sweat glands.
Patients with generalized autonomic neuropathies may report ataxia, gait instability, or near syncope/syncope. In addition, autonomic neuropathies have further symptoms that relate to the anatomic site of nerve damage—gastrointestinal, cardiovascular, bladder, or sudomotor.
– Gastrointestinal autonomic neuropathy may produce the following symptoms:
Dysphagia, abdominal pain, nausea/vomiting, malabsorption, faecal incontinence, diarrhoea, constipation.
– Cardiovascular autonomic neuropathy may produce the following symptoms :
Persistent sinus tachycardia, orthostatic hypotension, sinus arrhythmia, decreased heart variability in response to deep breathing, near syncope upon changing positions from recumbent to standing.
– Bladder neuropathy (which must be differentiated from prostate or spine disorders) may produce the following symptoms:
Poor urinary stream
Feeling of incomplete bladder emptying
Straining to void
– Sudomotor neuropathy may produce the following symptoms:
Heat intolerance
Heavy sweating of head, neck, and trunk with anhidrosis of lower trunk and extremities
Gustatory sweating

Criteria for the diagnosis of diabetes

1. A1C ≥6.5%. The test should be performed in a laboratory using a method that is certified and standardized.*
OR
2. Fasting glucose ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.*
OR
3. 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.*
OR
4. In a patient with classic symptoms of hyperglycaemia or hyperglycaemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycaemia, criteria 1–3 should be confirmed by repeat testing.

Prolactinomas, benign lesions that produce the hormone prolactin, are the most common hormone-secreting pituitary tumours.
Based on its size, a prolactinoma can be classified as a microprolactinoma (< 10 mm diameter) or a macroprolactinoma (>10 mm diameter). If the prolactinoma is large enough to compress the surrounding normal hormone-secreting pituitary cells, it may result in deficiencies of one or more hormones (e.g., thyroid-stimulating hormone [TSH], growth hormone [GH], adrenocorticotropic hormone). However, the patient has microadenoma so it is unlikely to cause compression manifestations.
Hyperprolactinemia inhibits GnRH secretion from the medial basal hypothalamus and LH release from the pituitary.

The patient has hyperprolactinaemia with otherwise normal oestradiol, FSH and LH. This is highly suggestive of Prolactinoma rather than a non functioning tumour.
In polycystic ovaries, there is increase in the level of LH while FSH is normal or low.

The empty boxes indicate that the patient has run out of his medication.
Chronic administration of high doses of glucocorticoids (GCs) (e.g., prednisone or prednisolone) and also other hormones such as oestrogens, progestins, androgens and growth hormone induce varying degrees of tolerance, resulting in a progressively decreased response to the effect of the drug, followed by dependence and rarely addiction.
The glucocorticoid withdrawal syndrome (GWS) has been considered a withdrawal reaction due to established physical dependence on supraphysiological GC levels.
The severity of GWS depends on the genetics and developmental history of the patient, on his environment, and on the phase and degree of dependence the patient has reached. Its management should include a temporary increase in the dose of GCs followed by gradual, slow tapering to a maintenance dose.

Rotterdam criteria for the diagnosis of polycystic ovary syndrome:
Two of the following three criteria are required:
1. Oligo/anovulation
2. Hyperandrogenism
– Clinical (hirsutism or less commonly male pattern alopecia) or
– Biochemical (raised FAI or free testosterone)
3. Polycystic ovaries on ultrasound
Other aetiologies must be excluded such as congenital adrenal hyperplasia, androgen-secreting tumours, Cushing syndrome, thyroid dysfunction and hyperprolactinaemia.
Cushing’s is excluded because there would have been marked obesity, hypertension and other related features.

RET (rearranged during transfection) is a receptor tyrosine kinase involved in the development of neural crest derived cell lineages, kidney, and male germ cells. Different human cancers, including papillary and medullary thyroid carcinomas, lung adenocarcinomas, and myeloproliferative disorders display gain-of-function mutations in RET.
In over 90% of cases, MEN2 syndromes are due to germline missense mutations of the RET gene.
Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumours, and pheochromocytoma.

The water deprivation test (i.e., the Miller-Moses test), is a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis. It is typically performed in patients with more chronic forms of Diabetes Insipidus (DI). The extent of deprivation is usually limited by the patient’s thirst or by any significant drop in blood pressure or related clinical manifestation of dehydration.

In healthy individuals, water deprivation leads to a urinary osmolality that is 2-4 times greater than plasma osmolality. Additionally, in normal, healthy subjects, administration of ADH produces an increase of less than 9% in urinary osmolality. The time required to achieve maximal urinary concentration ranges from 4-18 hours.

In central and nephrogenic DI, urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI. In primary polydipsia, urinary osmolality will be above 750 mOsm/kg after water deprivation.
A urinary osmolality that is 300-750 mOsm/kg after water deprivation and remains below 750 mOsm/kg after administration of ADH may be seen in partial central DI, partial nephrogenic DI, and primary polydipsia.

Achondroplasia is the most common type of short-limb disproportionate dwarfism. A single gene mapped to the short arm of chromosome 4 (band 4p16.3) is responsible for achondroplasia and is transmitted as an autosomal dominant trait. All people with achondroplasia have a short stature.
Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.
Examination of the infant after birth shows increased front-to-back head size. There may be signs of hydrocephalus. It may be diagnosed radiographically at birth, or becomes obvious within the first year with disparity between a large skull, normal trunk length and short limbs.