Carbimazole is the preferred initial treatment for Graves’ disease, especially in elderly patients or those with underlying cardiovascular disease and significant thyrotoxicosis, as evidenced by this patient’s symptoms and peripheral signs of Graves’ disease such as ophthalmopathy. Radioiodine treatment is not recommended as first-line therapy in these cases due to the increased risk of Graves’ ophthalmopathy. Adrenalectomy is the primary treatment for pheochromocytoma, while ketoconazole is used to manage excess cortisol production in conditions like Cushing’s. Hydrocortisone is part of the treatment plan for Addison’s Disease.

Management of Graves’ Disease

Despite numerous attempts, there is no clear consensus on the best way to manage Graves’ disease. The available treatment options include anti-thyroid drugs (ATDs), radioiodine treatment, and surgery. In recent years, ATDs have become the most popular first-line therapy for Graves’ disease. This is particularly true for patients who have significant symptoms of thyrotoxicosis or those who are at a high risk of hyperthyroid complications, such as elderly patients or those with cardiovascular disease.

To control symptoms, propranolol is often used to block the adrenergic effects. NICE Clinical Knowledge Summaries recommend that patients with Graves’ disease be referred to secondary care for ongoing treatment. If a patient’s symptoms are not controlled with propranolol, carbimazole should be considered in primary care.

ATD therapy involves starting carbimazole at 40mg and gradually reducing it to maintain euthyroidism. This treatment is typically continued for 12-18 months. The major complication of carbimazole therapy is agranulocytosis. An alternative regime, known as block-and-replace, involves starting carbimazole at 40mg and adding thyroxine when the patient is euthyroid. This treatment typically lasts for 6-9 months. Patients following an ATD titration regime have been shown to suffer fewer side-effects than those on a block-and-replace regime.

Radioiodine treatment is often used in patients who relapse following ATD therapy or are resistant to primary ATD treatment. However, it is contraindicated in pregnancy (should be avoided for 4-6 months following treatment) and in patients under the age of 16. Thyroid eye disease is a relative contraindication, as it may worsen the condition. The proportion of patients who become hypothyroid depends on the dose given, but as a rule, the majority of patients will require thyroxine supplementation after 5 years.

Weight gain is a common side effect of sulfonylureas.

Sulfonylureas are a type of medication used to treat type 2 diabetes mellitus. They work by increasing the amount of insulin produced by the pancreas, but they are only effective if the pancreas is functioning properly. Sulfonylureas bind to a specific channel on the cell membrane of pancreatic beta cells, which helps to increase insulin secretion. However, there are some potential side effects associated with these drugs.

One of the most common side effects of sulfonylureas is hypoglycaemia, which can be more likely to occur with long-acting preparations like chlorpropamide. Weight gain is another possible side effect. In rare cases, sulfonylureas can cause hyponatraemia, which is a condition where the body retains too much water and sodium levels become too low. Other rare side effects include bone marrow suppression, hepatotoxicity (liver damage), and peripheral neuropathy. It is important to note that sulfonylureas should not be used during pregnancy or while breastfeeding.

The patient’s hypertension, hypokalaemia, and hypernatremia suggest a diagnosis of hyperaldosteronism, where high levels of aldosterone cause increased water and sodium reabsorption in the kidneys and potassium loss. The recommended treatment for primary hyperaldosteronism due to bilateral adrenal disease is a mineralocorticoid antagonist, with spironolactone as the primary agent and eplerenone as an alternative. Losartan, an angiotensin receptor blocker, is an alternative to angiotensin-converting enzyme inhibitors for managing primary hypertension in patients under 55 years of age who are not Afro-Caribbean or diabetic. Nifedipine, a calcium-channel blocker, is a first-line drug for essential hypertension in patients aged 55 years or older or Afro-Caribbean patients. Perindopril, an ACEi, is a first-line drug for managing primary hypertension in patients under 55 years of age who are not Afro-Caribbean or diabetic. However, it is not appropriate for treating hyperaldosteronism, where spironolactone is the preferred option. Unilateral laparoscopic adrenalectomy is recommended for cases of hyperaldosteronism due to unilateral adrenal diseases, but not for bilateral adrenal disease like in this patient.

The patient is experiencing hyperthyroidism due to an excess of levothyroxine replacement. It is important to reduce the dose of levothyroxine and monitor the patient with regular blood tests until they become euthyroid again. Starting carbimazole or increasing the dose of levothyroxine is not recommended as it could lead to further complications. Propylthiouracil is only used in cases of thyrotoxic storm and radio-iodine therapy is not necessary in this case as the hyperthyroidism is due to over-replacement of levothyroxine.

Immediate initiation of insulin is recommended due to the high blood glucose levels and presence of macrosomia. Additionally, it is advisable to consider administering aspirin as there is an elevated risk of pre-eclampsia.

Gestational diabetes is a common medical disorder affecting around 4% of pregnancies. Risk factors include a high BMI, previous gestational diabetes, and family history of diabetes. Screening is done through an oral glucose tolerance test, and diagnostic thresholds have recently been updated. Management includes self-monitoring of blood glucose, diet and exercise advice, and medication if necessary. For pre-existing diabetes, weight loss and insulin are recommended, and tight glycemic control is important. Targets for self-monitoring include fasting glucose of 5.3 mmol/l and 1-2 hour post-meal glucose levels.

Anastrozole, an aromatase inhibitor, may lead to the development of osteoporosis. This medication is commonly used to treat oestrogen receptor-positive breast cancer in postmenopausal women by reducing the production of peripheral oestrogen. However, patients taking this medication are at an increased risk of developing osteoporosis. On the other hand, selective oestrogen receptor modulators (SERM) like tamoxifen may cause amenorrhoea, endometrial cancer, vaginal bleeding, and venous thromboembolism. Tamoxifen is typically used to treat oestrogen receptor-positive breast cancer in pre-menopausal women.

Anti-oestrogen drugs are used in the management of oestrogen receptor-positive breast cancer. Selective oEstrogen Receptor Modulators (SERM) such as Tamoxifen act as an oestrogen receptor antagonist and partial agonist. However, Tamoxifen can cause adverse effects such as menstrual disturbance, hot flushes, venous thromboembolism, and endometrial cancer. On the other hand, aromatase inhibitors like Anastrozole and Letrozole reduce peripheral oestrogen synthesis, which is important in postmenopausal women. Anastrozole is used for ER +ve breast cancer in this group. However, aromatase inhibitors can cause adverse effects such as osteoporosis, hot flushes, arthralgia, myalgia, and insomnia. NICE recommends a DEXA scan when initiating a patient on aromatase inhibitors for breast cancer.

Endocrine Disorders: Congenital Adrenal Hyperplasia, Conn Syndrome, Addisonian Crisis, Cushing Syndrome, and Thyrotoxic Crisis

Endocrine disorders are conditions that affect the production and regulation of hormones in the body. Here are five different endocrine disorders and their characteristics:

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive conditions caused by mutations in the enzymes involved in the production of steroids and hormones from the adrenal glands. It can affect both men and women equally, and symptoms include ambiguous genitalia at birth for women and hyperpigmentation and penile enlargement for men. Treatment involves hormone replacement therapy.

Conn Syndrome is a condition associated with primary hyperaldosteronism, which presents with hypernatraemia and hypokalaemia. It is more commonly seen in adult patients, but there are cases reported in childhood.

Addisonian Crisis occurs due to glucocorticoid and mineralocorticoid deficiency, usually occurring in adulthood. It is a potentially fatal episode that presents with hyponatraemia, hyperkalaemia, hypoglycaemia, and hypercalcaemia. Urgent intravenous administration of glucocorticoids is necessary for management.

Cushing Syndrome is due to cortisol excess, either exogenous or endogenous, and is usually diagnosed in adulthood. Symptoms include weight gain, hypertension, oedema, hyperglycaemia, hypokalaemia, and pigmentation of the skin in the axillae and neck.

Thyrotoxic Crisis, also known as a thyroid storm, is a life-threatening condition associated with excessive production of thyroid hormones. It can be the first presentation of undiagnosed hyperthyroidism in neonates and children. Symptoms include tachycardia, hypertension, fever, poor feeding, weight loss, diarrhoea, nausea, vomiting, seizures, and coma. Prompt treatment is necessary to prevent acute congestive heart failure, shock, and death.

Treatment of Diabetic Ketoacidosis: Continuing Long-Acting Insulin and Stopping Short-Acting Insulin

When a patient presents with diabetic ketoacidosis (DKA), it is important to provide prompt treatment. This involves fluid replacement with isotonic saline and an intravenous insulin infusion at 0.1 unit/kg per hour. While this takes place, the patient’s normal long-acting insulin should be continued, but their short-acting insulin should be stopped to avoid hypoglycemia.

In addition to insulin and fluid replacement, correction of electrolyte disturbance is essential. Serum potassium levels may be high on admission, but often fall quickly following treatment with insulin, resulting in hypokalemia. Potassium may need to be added to the replacement fluids, guided by the potassium levels. If the rate of potassium infusion is greater than 20 mmol/hour, cardiac monitoring is required.

Overall, the key to successful treatment of DKA is a careful balance of insulin, fluids, and electrolyte replacement. By continuing long-acting insulin and stopping short-acting insulin, healthcare providers can help ensure the best possible outcome for their patients.

Differential Diagnosis: Polyuria, Polydipsia, Constipation, and Loin-to-Groin Pain

Possible Causes and Clinical Features

Primary Hyperparathyroidism: This condition can cause hypercalcemia, leading to symptoms such as bone pain, osteopenia, kidney stones, constipation, nausea, vomiting, abdominal pain, fatigue, depression, and memory impairment. In severe cases, cardiac and metabolic disturbances, delirium, or coma may occur. Diagnosis is made by measuring serum-adjusted calcium and parathyroid hormone (PTH) levels at the same time.

Acute Pancreatitis: This condition can cause severe epigastric pain radiating to the back, vomiting, epigastric tenderness, ileus, and low-grade fever. Aetiological factors include alcohol and gallstones.

Addison’s Disease: This condition can cause generalised fatigue, abdominal pain, anorexia, nausea, vomiting, weight loss, ‘salt craving’, hyperpigmentation, vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia, hyponatraemia, and hyperkalaemia.

Anxiety Attack: This condition can cause chest pain, palpitations, nausea, vomiting, sweating, insomnia, flushing, tremor, and urinary frequency. It typically occurs in an individual who is excessively worried about a number of different events, causing increased tension.

Diabetic Ketoacidosis (DKA): This condition can cause polyuria, polydipsia, abdominal pain, Kussmaul respiration, and pear-drops-smelling breath.

Differential Diagnosis of Polyuria, Polydipsia, Constipation, and Loin-to-Groin Pain

Understanding Glycosylated Haemoglobin (HbA1c) in Diabetes Mellitus

Glycosylated haemoglobin (HbA1c) is a commonly used measure of long-term blood sugar control in diabetes mellitus. It is produced when glucose attaches to haemoglobin in the blood at a rate proportional to the glucose concentration. The level of HbA1c is influenced by the lifespan of red blood cells and the average blood glucose concentration. However, certain conditions such as sickle-cell anaemia, GP6D deficiency, and haemodialysis can interfere with accurate interpretation of HbA1c levels.

HbA1c is believed to reflect the blood glucose levels over the past 2-4 weeks, although it is generally thought to represent the previous 3 months. It is recommended that HbA1c be checked every 3-6 months until stable, then every 6 months. The Diabetes Control and Complications Trial (DCCT) has studied the complex relationship between HbA1c and average blood glucose. The International Federation of Clinical Chemistry (IFCC) has developed a new standardised method for reporting HbA1c in mmol per mol of haemoglobin without glucose attached.

Understanding HbA1c is crucial in managing diabetes mellitus and achieving optimal blood sugar control.