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.

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

Mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility. This is termed nonclassical adrenal hyperplasia.
Late-onset or nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence ranges from 1 in 30 to 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess.
Treatment needs to be directed toward the symptoms. Goals of treatment include normal linear growth velocity, a normal rate of skeletal maturation, ‘on-time’ puberty, regular menstrual cycles, prevention of or limited progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.
Normal Ultrasound rules out Turner’s syndrome.

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.

Thyroid malignancies are divided into papillary carcinomas (80%), follicular carcinomas (10%), medullary thyroid carcinomas (5-10%), anaplastic carcinomas (1-2%), primary thyroid lymphomas (rare), and primary thyroid sarcomas (rare).
Hürthle cell carcinoma is a rare thyroid malignancy that is often considered a variant of follicular carcinoma.
– Papillary and Follicular carcinoma are slow-growing tumours
– Sporadic cases of Medullary thyroid carcinoma also typically manifest with painless solitary thyroid nodules in the early stages.
– Anaplastic thyroid carcinoma has the most aggressive biologic behaviour of all thyroid malignancies and has one of the worst survival rates of all malignancies in general. It manifests as a rapidly growing thyroid mass in contrast to a well-differentiated carcinoma, which are comparatively slow-growing. Patients commonly present with associated symptoms due to local invasion. Hoarseness and dyspnoea resulting from the involvement of the recurrent laryngeal nerve and airway occur in as many as 50% of patients.
– Almost all patients with primary thyroid lymphoma have either a clinical history or histological evidence of chronic lymphocytic thyroiditis. The risk of primary thyroid lymphoma increases 70-fold in patients with chronic lymphocytic thyroiditis compared with the general population. Regional and distant lymphadenopathy is common.

This child has pseudo hypoparathyroidism. It is a heterogeneous group of rare endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcaemia, hyperphosphatemia, and increased serum concentration of PTH.
Patients with pseudo hypoparathyroidism type 1a present with a characteristic phenotype collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:
Short stature
Stocky habitus
Obesity
Developmental delay
Round face
Dental hypoplasia
Brachymetacarpals
Brachymetatarsals
Soft tissue calcification/ossification
The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalcaemia and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodelling and lead to hyper-parathyroid bone disease.
The goals of pharmacotherapy are to correct calcium deficiency, to prevent complications, and to reduce morbidity. Intravenous calcium is the initial treatment for all patients with severe symptomatic hypocalcaemia. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of pseudo hypoparathyroidism.

Exposure to excessive androgens is usually accompanied by premature epiphyseal maturation and closure, resulting in a final adult height that is typically significantly below that expected from parental heights.

congenital adrenal hyperplasia (CAH) is associated with precocious puberty caused by long term exposure to androgens, which activate the hypothalamic-pituitary-gonadal axis. Similarly, CAH is associated with hyperpigmentation and hyperreninemia due to sodium loss and hypovolaemia.

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.

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

The patient has Acromegaly.
Acromegaly is a chronic disorder characterised by growth hormone (GH) hypersecretion, predominantly caused by a pituitary adenoma.

Random GH level testing is not recommended for diagnosis given the pulsatile nature of secretion. Stress, physical exercise, acute critical illness and fasting state can cause a physiological higher peak in GH secretion.

Pegvisomant is a US Food and Drug Administration-approved treatment for use after surgery. In a global non-interventional safety surveillance study, pegvisomant normalised IGF-1 in 67.5% of patients after 5 years (most likely due to lack of dose-up titration), and also improved clinical symptoms. Pegvisomant improves insulin sensitivity, and long-term follow-up showed significantly decreased fasting glucose over time, while the first-generation SRL only have a marginal clinical impact on glucose homeostasis in acromegaly. Pegvisomant does not have any direct anti-proliferative effects on pituitary tumour cells, but tumour growth is rare overall.

Insulin remains the standard of care for the treatment of uncontrolled gestational diabetes. Tight control maintained in the first trimester and throughout pregnancy plays a vital role in decreasing poor fetal outcomes, including structural anomalies, macrosomia, hypoglycaemia of the new-born, adolescent and adult obesity, and diabetes.
The baby is already large for dates so nutritional therapy can not be used alone.

Raloxifene is a selective oestrogen-receptor modulator (SERM) that has been approved for use in the prevention and treatment of osteoporosis in postmenopausal women.
A SERM interacts with oestrogen receptors, functioning as an agonist in some tissues and an antagonist in other tissues. Because of their unique pharmacologic properties, these agents can achieve the desired effects of oestrogen without the possible stimulatory effects on the breasts or uterus.

Euthyroid sick syndrome (also known as nonthyroidal illness syndrome) can be described as abnormal findings on thyroid function tests that occurs in the setting of a nonthyroidal illness (NTI), without pre-existing hypothalamic-pituitary and thyroid gland dysfunction. After recovery from an NTI, these thyroid function test result abnormalities should be completely reversible.
Multiple alterations in serum thyroid function test findings have been recognized in patients with a wide variety of NTIs without evidence of pre-existing thyroid or hypothalamic-pituitary disease. The most prominent alterations are low serum triiodothyronine (T3) and elevated reverse T3 (rT3), leading to the general term low T3 syndrome. Thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 (FT4), and free T4 index (FTI) also are affected in variable degrees based on the severity and duration of the NTI. As the severity of the NTI increases, both serum T3 and T4 levels drop, but they gradually normalize as the patient recovers.
Reverse T3 is used to differentiate between this condition and secondary thyroid failure.

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

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.

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).

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.

Several dipeptidyl peptidase-4 (DPP-4) inhibitors are in clinical development; these are orally active and increase levels of active glucagon-like peptide-1 (GLP-1), which in turn increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels.
Sitagliptin and vildagliptin both have a long duration of action, allowing once-daily administration. Both sitagliptin and vildagliptin are safe and tolerable with a low risk of hypoglycaemia. In drug-naïve subjects with type 2 diabetes, both sitagliptin and vildagliptin reduce A1C levels by ,1% as monotherapy.

During pregnancy, profound changes in thyroid physiology occur to provide sufficient thyroid hormone (TH) to both the mother and foetus. This is particularly important during early pregnancy because the fetal thyroid starts to produce considerable amounts of TH only from approximately 20 weeks of gestation, until which time the foetus heavily depends on the maternal supply of TH. This supply of TH to the foetus, as well as increased concentrations of TH binding proteins (thyroxine-binding globulin) and degradation of TH by placental type 3 iodothyronine deiodinase, necessitate an increased production of maternal TH. This requires an intact thyroid gland and adequate availability of dietary iodine and is in part mediated by the pregnancy hormone human chorionic gonadotropin, which is a weak agonist of the thyroid-stimulating hormone (TSH) receptor. As a consequence, serum-free thyroxine (FT4) concentrations increase and TSH concentrations decrease from approximately the eighth week throughout the first half of pregnancy, resulting in different reference intervals for TSH and FT4 compared to the non-pregnant state.

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).