Endocrinology

Hypothyroidism This is a common condition characterised by a lack of thyroid hormone. The issue is that it gives non-specific symptoms which are very subtle, and so can be tricky to diagnose. However, if treated, the prognosis is excellent. Symptoms are mostly related to the magnitude of the thyroid hormone deficiency   Symptoms Increased weight with normal appetite Cold intolerance with no sweating Bradycardia Decreased mood Constipation Tiredness and lethargic Poor memory/cognition   Signs Slow reflexes and ataxia Cold dry hands Ascites/oedema Hypercholesterolemia Heavy Periods (menorrhagia) Absent Reflexes Carpal Tunnel Syndrome   Management Levothyroxine (hormone replacement therapy) to replace T4.

Multiple Endocrine Neoplasia This is an inherited autosomal dominant condition that leads to multiple hormoneproducing tumours in endocrine glands. It is divided into three types: Type 1 is due to a mutation in the MEN1 tumour suppressor gene. In type 1, the most common presentation is hypercalcaemia due to parathyroid hyperplasia Type 2 is due to a RET oncogene (receptor tyrosine kinase) mutation and is further divided into 2 types.   Multiple Endocrine Neoplasia – Type 1 This is a subtype which consists of the following. 3Ps: Parathyroid hyperplasia, without altering hormone secretion. Pituitary prolactinoma/GH tumour – Most of these

Posterior pituitary gland   Diabetes insipidus (DI) This is a condition characterised by the production of large volumes of dilute urine, which occurs due to poor water reabsorption by the kidney.   Central/Neurogenic DI This refers to a failure of the pituitary gland to produce ADH. It can occur idiopathically, due to a congenital defect in the ADH gene or secondary to central nervous system trauma (e.g., following neurosurgery) and tumours. It is responsive to desmopressin treatment.   Nephrogenic DI This is when the kidneys are unable to respond to ADH. This can be due to genetic mutations in the

Pheochromocytoma This is an adrenaline producing tumour of the chromaffin cells. It follows rule of 10’s – 10% bilateral, 10% familial, 10% malignant and 10% located outside adrenal gland in the bladder wall or organ of Zuckerandl by aortic bifurcation. It is associated with the conditions like MEN 2A/B and neurofibromatosis type 1. It is also seen in von Hippel-Lindau disease, an autosomal dominant hereditary condition characterised by tumours arising in multiple organs.   Symptoms Triad of episodic headache, sweating and tachycardia (palpitations) Hypertension, which may be resistant to treatment   Key tests Blood tests show increased plasma metanephrine levels

Hypothyroidism This is a common condition characterised by a lack of thyroid hormone. The issue is that it gives non-specific symptoms which are very subtle, and so can be tricky to diagnose. However, if treated, the prognosis is excellent. Symptoms are mostly related to the magnitude of the thyroid hormone deficiency   Symptoms Increased weight with normal appetite Cold intolerance with no sweating Bradycardia Decreased mood Constipation Tiredness and lethargic Poor memory/cognition   Signs Slow reflexes and ataxia Cold dry hands Ascites/oedema Hypercholesterolemia Heavy Periods (menorrhagia) Absent Reflexes Carpal Tunnel Syndrome   Management Levothyroxine (hormone replacement therapy) to replace T4.

  Hypoparathyroidism This is a condition characterised by low levels of parathyroid hormone. Symptoms occur due to the hypocalcaemia raising excitability of nerve and muscle.   Primary hypoparathyroidism This refers to low levels of PTH due to an impairment in PTH secretion. It can primary due to autoimmune damage, congenital DiGeorge syndrome or secondary to other causes, e.g., surgery or low Mg2+ (needed for synthesis). Symptoms Muscle twitching, tetany, cramping and spasm Numbness and tingling around mouth Can lead to seizures Chvostek sign – a clinical sign where tapping on the zygomatic bone causes twitching of facial muscles   Key tests

Hypothyroidism This is a common condition characterised by a lack of thyroid hormone. The issue is that it gives non-specific symptoms which are very subtle, and so can be tricky to diagnose. However, if treated, the prognosis is excellent. Symptoms are mostly related to the magnitude of the thyroid hormone deficiency   Symptoms Increased weight with normal appetite Cold intolerance with no sweating Bradycardia Decreased mood Constipation Tiredness and lethargic Poor memory/cognition   Signs Slow reflexes and ataxia Cold dry hands Ascites/oedema Hypercholesterolemia Heavy Periods (menorrhagia) Absent Reflexes Carpal Tunnel Syndrome   Management Levothyroxine (hormone replacement therapy) to replace T4.

Posterior pituitary gland   Diabetes insipidus (DI) This is a condition characterised by the production of large volumes of dilute urine, which occurs due to poor water reabsorption by the kidney.   Central/Neurogenic DI This refers to a failure of the pituitary gland to produce ADH. It can occur idiopathically, due to a congenital defect in the ADH gene or secondary to central nervous system trauma (e.g., following neurosurgery) and tumours. It is responsive to desmopressin treatment.   Nephrogenic DI This is when the kidneys are unable to respond to ADH. This can be due to genetic mutations in the

Hypoparathyroidism This is a condition characterised by low levels of parathyroid hormone. Symptoms occur due to the hypocalcaemia raising excitability of nerve and muscle.   Primary hypoparathyroidism This refers to low levels of PTH due to an impairment in PTH secretion. It can primary due to autoimmune damage, congenital DiGeorge syndrome or secondary to other causes, e.g., surgery or low Mg2+ (needed for synthesis). Symptoms Muscle twitching, tetany, cramping and spasm Numbness and tingling around mouth Can lead to seizures Chvostek sign – a clinical sign where tapping on the zygomatic bone causes twitching of facial muscles   Key tests Blood

Type 1 Diabetes This is a condition in which there is autoimmune destruction of pancreatic beta-cells leading to an inability to produce endogenous insulin. T lymphocytes attack the islets and autoantibodies against insulin can be present. It is associated with HLA-DR3 and HLA-DR4. The disease usually manifests in adolescence, sometimes after a viral infection.   Symptoms Polyuria, polydipsia, and glycosuria, due to hyperglycaemia Weight loss, as unopposed glucagon leads to lipolysis and glycogenolysis Can be asymptomatic and lead to life threatening complications   Management The mainstay of treatment is insulin to control blood glucose levels Insulin regimes vary according to

Posterior pituitary gland   Diabetes insipidus (DI) This is a condition characterised by the production of large volumes of dilute urine, which occurs due to poor water reabsorption by the kidney.   Central/Neurogenic DI This refers to a failure of the pituitary gland to produce ADH. It can occur idiopathically, due to a congenital defect in the ADH gene or secondary to central nervous system trauma (e.g., following neurosurgery) and tumours. It is responsive to desmopressin treatment.   Nephrogenic DI This is when the kidneys are unable to respond to ADH. This can be due to genetic mutations in the

Type 1 Diabetes This is a condition in which there is autoimmune destruction of pancreatic beta-cells leading to an inability to produce endogenous insulin. T lymphocytes attack the islets and autoantibodies against insulin can be present. It is associated with HLA-DR3 and HLA-DR4. The disease usually manifests in adolescence, sometimes after a viral infection.   Symptoms Polyuria, polydipsia, and glycosuria, due to hyperglycaemia Weight loss, as unopposed glucagon leads to lipolysis and glycogenolysis Can be asymptomatic and lead to life threatening complications   Management The mainstay of treatment is insulin to control blood glucose levels Insulin regimes vary according to

Type 1 Diabetes This is a condition in which there is autoimmune destruction of pancreatic beta-cells leading to an inability to produce endogenous insulin. T lymphocytes attack the islets and autoantibodies against insulin can be present. It is associated with HLA-DR3 and HLA-DR4. The disease usually manifests in adolescence, sometimes after a viral infection.   Symptoms Polyuria, polydipsia, and glycosuria, due to hyperglycaemia Weight loss, as unopposed glucagon leads to lipolysis and glycogenolysis Can be asymptomatic and lead to life threatening complications   Management The mainstay of treatment is insulin to control blood glucose levels Insulin regimes vary according to

Pheochromocytoma This is an adrenaline producing tumour of the chromaffin cells. It follows rule of 10’s – 10% bilateral, 10% familial, 10% malignant and 10% located outside adrenal gland in the bladder wall or organ of Zuckerandl by aortic bifurcation. It is associated with the conditions like MEN 2A/B and neurofibromatosis type 1. It is also seen in von Hippel-Lindau disease, an autosomal dominant hereditary condition characterised by tumours arising in multiple organs.   Symptoms Triad of episodic headache, sweating and tachycardia (palpitations) Hypertension, which may be resistant to treatment   Key tests Blood tests show increased plasma metanephrine levels

Pheochromocytoma This is an adrenaline producing tumour of the chromaffin cells. It follows rule of 10’s – 10% bilateral, 10% familial, 10% malignant and 10% located outside adrenal gland in the bladder wall or organ of Zuckerandl by aortic bifurcation. It is associated with the conditions like MEN 2A/B and neurofibromatosis type 1. It is also seen in von Hippel-Lindau disease, an autosomal dominant hereditary condition characterised by tumours arising in multiple organs.   Symptoms Triad of episodic headache, sweating and tachycardia (palpitations) Hypertension, which may be resistant to treatment   Key tests Blood tests show increased plasma metanephrine levels

Posterior pituitary gland   Diabetes insipidus (DI) This is a condition characterised by the production of large volumes of dilute urine, which occurs due to poor water reabsorption by the kidney.   Central/Neurogenic DI This refers to a failure of the pituitary gland to produce ADH. It can occur idiopathically, due to a congenital defect in the ADH gene or secondary to central nervous system trauma (e.g., following neurosurgery) and tumours. It is responsive to desmopressin treatment.   Nephrogenic DI This is when the kidneys are unable to respond to ADH. This can be due to genetic mutations in the

  The pituitary gland is one of the most important endocrine glands in the body. It interacts with the hypothalamus which stimulates the production of hormones from the pituitary. It is split into 2 parts:   Posterior pituitary This is a down-growth of the brain contained within the blood brain barrier which releases 2 hormones:   a) ADH This controls the water content on the body by influencing water reabsorption from collecting duct. – Binds V1 receptors on artieroles (vasoconstriction) + V2 receptors on collecting duct – N.B. Ethanol inhibits ADH secretion, explains why you need to urinate (“Break the

The adrenal gland is split into the adrenal medulla and the cortex, which itself is subdivided into 3 sections. The glands are found above the kidneys and are supplied by superior, middle and inferior adrenal arteries. Medulla This is at the centre of each adrenal gland. – Made up of chromaffin cells producing noradrenaline (20%) and adrenaline (80%) – Driven by sympathetic preganglionic fibres which synapse in medulla – Considered a specialised sympathetic ganglion which releases secretions into the blood.   Cortex This is the outermost layer of the adrenal gland which is split into 3 zones: i) Zona glomerulosa

Thyroid Gland The thyroid gland is an endocrine gland in the neck. It is made of two lobes joined together by an isthmus. It is made up of two types of cells which control metabolic rate and calcium levels in the body.   a) Parafollicular cells – Secrete Calcitonin, which antagonizes effects of PTH – Decreases plasma [Ca2+] by decreasing bone breakdown by inhibiting osteoclasts whilst promoting osteoblasts   b) Follicular cells – Produce thyroid hormones, triiodothyronine (T3) and thyroxine (T4) – tyrosine based hormones partially composed of iodine. – Mainly produces T4 which is 5x less active than T3 – 85% of T3 is

The normal blood glucose in the body is 4-6mM and is controlled by pancreatic hormones insulin and glucagon. – It is important to control these as certain organs like the brain can only use glucose as a respiratory substrate. – Normally glucose –> broken down by glycolysis –> enters Krebs cycle –> oxidative phosphorylation.   Some cells can also metabolize fat. This produces reduced FAD/NAD which enter oxidative phosphorylation. But some organs like the brain cannot break down fat and instead use ketone bodies which are made in the liver.  These ketone bodies are an alternative fuel source – They

Multiple Endocrine Neoplasia This is an inherited autosomal dominant condition that leads to multiple hormoneproducing tumours in endocrine glands. It is divided into three types: Type 1 is due to a mutation in the MEN1 tumour suppressor gene. In type 1, the most common presentation is hypercalcaemia due to parathyroid hyperplasia Type 2 is due to a RET oncogene (receptor tyrosine kinase) mutation and is further divided into 2 types.   Multiple Endocrine Neoplasia – Type 1 This is a subtype which consists of the following. 3Ps: Parathyroid hyperplasia, without altering hormone secretion. Pituitary prolactinoma/GH tumour – Most of these

Posterior pituitary gland   Diabetes insipidus (DI) This is a condition characterised by the production of large volumes of dilute urine, which occurs due to poor water reabsorption by the kidney.   Central/Neurogenic DI This refers to a failure of the pituitary gland to produce ADH. It can occur idiopathically, due to a congenital defect in the ADH gene or secondary to central nervous system trauma (e.g., following neurosurgery) and tumours. It is responsive to desmopressin treatment.   Nephrogenic DI This is when the kidneys are unable to respond to ADH. This can be due to genetic mutations in the

Pheochromocytoma This is an adrenaline producing tumour of the chromaffin cells. It follows rule of 10’s – 10% bilateral, 10% familial, 10% malignant and 10% located outside adrenal gland in the bladder wall or organ of Zuckerandl by aortic bifurcation. It is associated with the conditions like MEN 2A/B and neurofibromatosis type 1. It is also seen in von Hippel-Lindau disease, an autosomal dominant hereditary condition characterised by tumours arising in multiple organs.   Symptoms Triad of episodic headache, sweating and tachycardia (palpitations) Hypertension, which may be resistant to treatment   Key tests Blood tests show increased plasma metanephrine levels

  Hypoparathyroidism This is a condition characterised by low levels of parathyroid hormone. Symptoms occur due to the hypocalcaemia raising excitability of nerve and muscle.   Primary hypoparathyroidism This refers to low levels of PTH due to an impairment in PTH secretion. It can primary due to autoimmune damage, congenital DiGeorge syndrome or secondary to other causes, e.g., surgery or low Mg2+ (needed for synthesis). Symptoms Muscle twitching, tetany, cramping and spasm Numbness and tingling around mouth Can lead to seizures Chvostek sign – a clinical sign where tapping on the zygomatic bone causes twitching of facial muscles   Key tests

Hypothyroidism This is a common condition characterised by a lack of thyroid hormone. The issue is that it gives non-specific symptoms which are very subtle, and so can be tricky to diagnose. However, if treated, the prognosis is excellent. Symptoms are mostly related to the magnitude of the thyroid hormone deficiency   Symptoms Increased weight with normal appetite Cold intolerance with no sweating Bradycardia Decreased mood Constipation Tiredness and lethargic Poor memory/cognition   Signs Slow reflexes and ataxia Cold dry hands Ascites/oedema Hypercholesterolemia Heavy Periods (menorrhagia) Absent Reflexes Carpal Tunnel Syndrome   Management Levothyroxine (hormone replacement therapy) to replace T4.

Diabetic Ketoacidosis This is an emergency which is characterised by severe hyperglycaemia and severe acidosis, seen in diabetes. It occurs due to lack of insulin, meaning patients cannot metabolise glucose and so the body responds by producing ketone bodies.   Symptoms Polyuria, polydipsia Abdominal pain Nausea/vomiting Ketotic breath Compensatory deep breathing (Kussmaul hyperventilation) Can cause confusion and seizures Key tests Blood gas shows acidosis (venous pH < 7.3 or HCO3– > 15 mM) Blood glucose shows hyperglycaemia Blood ketones > 3 mM or > 2 on a urine dipstick   Management Start fluid infusion, e.g., 0.9% normal saline Fixed rate IV

Type 1 Diabetes This is a condition in which there is autoimmune destruction of pancreatic beta-cells leading to an inability to produce endogenous insulin. T lymphocytes attack the islets and autoantibodies against insulin can be present. It is associated with HLA-DR3 and HLA-DR4. The disease usually manifests in adolescence, sometimes after a viral infection.   Symptoms Polyuria, polydipsia, and glycosuria, due to hyperglycaemia Weight loss, as unopposed glucagon leads to lipolysis and glycogenolysis Can be asymptomatic and lead to life threatening complications   Management The mainstay of treatment is insulin to control blood glucose levels Insulin regimes vary according to

Overview The thyroid is an endocrine gland responsible for the production of thyroid hormones T3 and T4. The major functional cells of the thyroid are the follicular cells. These are arranged into spheres that form a functional unit termed a follicle. Within these follicles is a central lumen containing colloid; the extracellular storage site for thyroid hormone. Colloid is composed largely of thyroglobulin (Tg) a glycoprotein involved in thyroid hormone synthesis. Parafollicular C cells secrete calcitonin, a hormone involved in calcium regulation. H-P-T axis Thyroid hormone release is controlled by the hypothalamic-pituitary-thyroid axis. 1. Thyrotropin releasing hormone TRH is secreted from the

Overview The syndrome of inappropriate anti-diuretic hormone (SIADH) results from excess ADH secretion. ADH excess, as the name suggests, results in reduced diuresis – water excretion and urinary output are reduced. This leads to an increase in total body water and hyponatraemia. The condition is common and has an enormous number of causes. Once recognised fluid restriction is the mainstay of management with careful monitoring of plasma sodium levels. NOTE: Osmolality is a measure of osmoles of solute per kilogram of solvent (Osm/kg). Physiology ADH release is governed by the plasma osmolality. Antidiuretic hormone (ADH) is produced by the magnocellular neurons in the paraventricular

Overview Primary hyperparathyroidism (PHPT) is characterised by excess production of parathyroid hormone (PTH) by one or more parathyroid glands resulting in elevated serum calcium. The condition is most commonly related to a parathyroid adenoma (80-85% of cases) or parathyroid hyperplasia. Rarely it is related to a parathyroid carcinoma. PTH is a key hormone involved in calcium and phosphate homeostasis, its excess leads to elevated serum calcium. PHPT is the most common cause of hypercalcaemia in the general population. Parathyroidectomy offers excellent chance of cure in patients who meet the indications for surgery. Types of hyperparathyroidism Although this note focuses on primary hyperparathyroidism, it

Overview Primary aldosteronism is a condition caused by an excess of the adrenal hormone aldosterone independent of the renin-angiotensin-aldosterone axis. The hallmarks of disease are hypertension and hypokalaemia – though hypokalaemia is often absent. Primary aldosteronism is increasingly being recognised as a common and under-diagnosed cause of secondary hypertension. Today prevalence is thought to be between 5-15% of patients with hypertension. Disease is caused by one of a number of subtypes: Bilateral idiopathic hyperaldosternism (60-70%) Aldosterone-producing adenoma (30-40%) Unilateral hyperplasia (approx 3%) Other (familial hyperaldosteronism, adrenal carcinoma) Treatment depends on the underlying cause and whether it is unilateral or bilateral. It may involve surgery (adrenalectomy) or aldosterone

Overview Phaeochromocytoma refers to a catecholamine-secreting tumour of chromaffin cells. Chromaffin cells are a type of neuroendocrine cell that are involved in the formation and release of catecholamines, which include noradrenaline, adrenaline and dopamine. These hormones have an important role in the sympathetic nervous system as part of the ‘fight-or-flight’ response. Chromaffin cells are predominantly found in the adrenal medulla, but also in the sympathetic paravertebral ganglia of the thorax, abdomen, and pelvis. Catecholamine-secreting tumours Catecholamine-secreting tumours may arise from the adrenal medulla or from the sympathetic ganglia and are known as phaeochromocytomas and paragangliomas respectively: Phaechromocytoma: arising from the adrenal medulla, accounts for

Introduction Multiple endocrine neoplasia (MEN) syndromes are autosomal dominantly inherited conditions characterised by tumours of endocrine glands. Multiple endocrine neoplasia (MEN) type 1 and 2 are rare autosomal dominant disorders characterised by benign and malignant changes in multiple endocrine glands: MEN type 1: is caused by a mutation to the MEN 1 tumour suppressor gene and is characterised by the three P’s; primary hyperparathyroidism, pituitary adenoma and pancreatic tumours. MEN type 2: is caused by a mutation of the RET proto-oncogene, it is characterised by primary hyperparathyroidism (less common and milder than in type 1), phaeochromocytomas and medullary thyroid cancer. It is

Definition & classification Hyperthyroidism is a common endocrine condition caused by an overactive thyroid gland causing an excess of thyroid hormone. Hyperthyroidism affects around 1-2% of the population. It is important to first define the terminology: Hyperthyroidism: overactive thyroid gland (i.e. increased thyroid hormone production) causing an excess of thyroid hormone and thyrotoxicosis. Thyrotoxicosis: refers to an excess of thyroid hormone, having an overactive thyroid gland is not a prerequisite (e.g. ingestion of excess thyroid hormone). Hyperthyroidism more commonly affects women than men (5-10 times more common) and may be associated with a number of autoimmune and endocrine conditions. In this note,

Introduction Diabetes insipidus results from a deficiency of, or resistance to, anti-diuretic hormone. Anti-diuretic hormone (ADH) is a hormone synthesised in the hypothalamus and released by the posterior pituitary. Its release is triggered by a rise in plasma osmolality and its action is to cause reabsorption of water in the kidneys. The clinical consequence of an inadequate ADH response, as seen in diabetes insipidus, is an inability to concentrate urine with resulting polyuria (increased urine) and polydipsia (increased thirst). DI is a rare condition with a prevalence estimated to be 1 in 25,000. There are two major forms: Central (CDI): caused by

Introduction Cushing’s syndrome is caused by prolonged exposure to an excess of glucocorticoids. Clinical features depend on the duration of disease and degree of cortisol excess but include weight gain, skin changes, menstrual irregularities, glucose intolerance and mood disturbance. The cause may be endogenous or exogenous: Exogenous: i.e. derived externally – occurs due to the administration of glucocorticoids either as a medication or misuse. This is by far the most common cause. Endogenous: i.e. derived internally – occurs due to excess production of glucocorticoids by the body itself. This is very rare (estimated at 5 in 1,000,000). Cushing’s disease, which refers

Introduction Addison’s disease (primary adrenal insufficiency) is caused by destruction or dysfunction of the adrenal cortex. The adrenal glands sit atop each kidney, they are an important endocrine organ responsible for the release of catecholamines (adrenaline, noradrenaline), glucocorticoids, mineralocorticoids and sex hormones. Adrenal insufficiency occurs when there is a reduction of glucocorticoid +/- mineralocorticoid production such that normal physiology is interrupted: Primary adrenal insufficiency (Addison’s disease): caused by destruction or dysfunction of the adrenal cortex. This is the focus of this note. Secondary adrenal insufficiency: caused by a reduction in adrenocorticotropic hormone release. May be seen as part of panhypopituitarism, an isolated deficiency, following brain

Overview Acromegaly is a condition caused by an excess of growth hormone (GH) most commonly related to a pituitary adenoma. It tends to present with macrognathia, frontal bossing and enlargement of hands and feet. Presentation may also be related to the aetiology – e.g. mass effect of a pituitary adenoma resulting in visual field defects and headache. It is associated with a number of systemic conditions (e.g. cardiovascular disease, diabetes). The condition is thought to be rare though the true prevalence is hard to establish. Recent studies estimate a prevalence of up to 1 in 1000 individuals in patients who were randomly screened.