Dopamine is a neurotransmitter and amine hormone that is derived from the amino acid tyrosine. It is made in a number of places throughout the human body, both inside and outside the central nervous system. The adrenal medulla, dopamine neurons in the arcuate nucleus of the hypothalamus, the substantia nigra, and other areas of the brain produce dopamine.

The tuberoinfundibular pathway refers to the dopamine neurons in the arcuate nucleus of the hypothalamus’ tubeal region. Dopamine is discharged into the hypothalamo-hypophyseal portal system from these neurons’ neurosecretory terminals at the median eminence.

The major function of dopamine produced from the hypothalamus is to suppress prolactin production from the anterior pituitary, and it is released in reaction to excessive levels of prolactin secretion. Modulation of motor-control centres and activation of reward centres are two more crucial activities of the brain.
Dopamine-secreting cells can also be found in other areas of the body, where they perform mostly paracrine functions (acting on nearby cells).

When there are excessive circulating levels of aldosterone, hyperaldosteronism occurs. There are two main types of hyperaldosteronism:

Primary hyperaldosteronism (,95% of cases)
Secondary hyperaldosteronism (,5% of cases)

Primary causes of hyperaldosteronism include:
Adrenal adenoma (Conn’s syndrome)
Adrenal hyperplasia
Adrenal cancer
Familial aldosteronism
Secondary causes of hyperaldosteronism include:
Drugs
Obstructive renal artery disease
Renal vasoconstriction
Oedematous disorders syndrome

Adrenal adenoma is the commonest cause of hyperaldosteronism (seen in ,80% of all cases).

Glucagon binds to class B G-protein coupled receptors and activates adenylate cyclase, increasing cAMP intracellularly.

This activates protein kinase A. Protein kinase A phosphorylates and activates important enzymes in target cells.

A history of recent weight loss is very suggestive of an absolute deficiency of insulin seen in type I diabetes mellitus.

An age of onset of less than 20 years makes a diagnosis of type I diabetes mellitus more likely. However, an increasing number of obese children and young people are being diagnosed with type II diabetes.

Microalbuminuria, peripheral neuropathy, and retinopathy all occur in both type I and type II diabetes mellitus. They are not more suggestive of type I DM.

Corticotropin-releasing hormone (CRH) is a neurotransmitter and peptide hormone. It is generated by cells in the hypothalamic paraventricular nucleus (PVN) and released into the hypothalamo-hypophyseal portal system at the median eminence through neurosecretory terminals of these neurons. Stress causes the release of CRH.

The CRH is carried to the anterior pituitary through the hypothalamo-hypophyseal portal system, where it activates corticotrophs to release adrenocorticotropic hormone (ACTH). Cortisol, glucocorticoids, mineralocorticoids, and DHEA are all produced in response to ACTH.

Excessive CRH production causes the size and quantity of corticotrophs in the anterior pituitary to expand, which can lead to the creation of a corticotrope tumour that generates too much ACTH.

Calcium is stored in bones for nearly all of the body’s calcium, but it is also found in some cells (most notably muscle cells) and the blood. The average adult diet comprises roughly 25 mmol of calcium per day, of which the body absorbs only about 5 mmol.

Parathyroid hormone (PTH), a polypeptide containing 84 amino acids, is the principal hormone that controls free calcium in the body.

Its main actions are:
Increases osteoclastic activity
Increases plasma calcium concentration
Decreases renal phosphate reabsorption
Decreases plasma phosphate concentration
Increases renal tubular reabsorption of calcium
Increases calcium and phosphate absorption in the small intestine
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol

The only mechanism by which insulin facilitates uptake of glucose into cells is by facilitated diffusion through a family of hexose transporters.

The major transporter used for glucose uptake is GLUT4. GLUT4 is made available in the plasma membrane by the action of insulin.
When insulin concentrations are low, GLUT4 transporters are present in cytoplasmic vesicles, where they are cannot be used for transporting glucose.

A thyroid function test is used in the diagnosis of hyperthyroidism.
Serum TSH should be the first-line investigation for patients with suspected hyperthyroidism as it has the highest sensitivity and specificity for hyperthyroidism.

A normal TSH level almost always excludes the diagnosis, though there are rare exceptions to this.

Antithyroglobulin antibodies are commonly present in Graves’ disease, but the test has a sensitivity of 98% and specificity of 99, and is not widely available.

Radioactive iodine uptake scan using iodine-123 – shows low uptake in thyroiditis but high in Graves’ disease and toxic multinodular goitre. It is however, not first-line investigation in this case

Thyroid ultrasound scan – is a cost-effective and safe alternative to the radioactive iodine uptake scan.

Approximately half of total serum calcium is in the free or ionised Ca2+ state, 40% is attached to plasma proteins (mostly albumin), and the remaining 10% is in complexes with organic ions like citrate and phosphate. The ionized form is the only one that works.

Glucagon, a peptide hormone, is produced and secreted by alpha cells of the islets of Langerhans, located in the endocrine portion of the pancreas.

Its main physiological role is stimulation of hepatic glucose output leading to increase in blood glucose. It is the major counter-regulatory hormone to insulin in maintaining glucose homeostasis.

The principal stimulus for the secretion of glucagon is hypoglycaemia. Hypoglycaemia then stimulates:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue leading to increased glycaemia.

Secretion of glucagon is also stimulated by arginine, alanine, adrenaline, acetylcholine and cholecystokinin

Secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

The anterior pituitary gland produces and secretes a peptide hormone called adrenocorticotropic hormone (ACTH) (adenohypophysis). It is secreted in response to the hypothalamus’s secretion of the hormone corticotropin-releasing hormone (CRH).

ACTH promotes cortisol secretion via binding to cell surface ACTH receptors in the zona fasciculata of the adrenal cortex.

ACTH also promotes the production of beta-endorphin, which is a precursor to melanocyte-releasing hormone (MRH).

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

Hormones can be classified into three categories depending on their chemical composition: amines, peptides (and proteins), and steroids. Amines are made up of single amino acids (for example, tyrosine), peptide hormones are made up of peptides (or proteins), and steroid hormones are made up of cholesterol.
The table below lists some prominent instances of each of these three hormone classes:

1. Peptide hormone:
Adrenocorticotropic hormone (ACTH)
Prolactin
Vasopressin
Oxytocin
Glucagon
Insulin
Somatostatin
Cholecystokinin

2. Amine hormone:
Adrenaline (epinephrine)
Noradrenaline (norepinephrine)
Dopamine

3. Steroid hormone:
Mineralocorticoids (e.g. aldosterone)
Glucocorticoids (e.g. cortisol)
Progestogens
Androgens
Oestrogens

1-alpha-hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the kidney.

The key regulatory point in the formation of 1,25-dihydroxycholecalciferol is 1-alpha-hydroxylase, which is promoted by parathyroid hormone or hypophosphatemia.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids.

Iatrogenic corticosteroid injection is the most prevalent cause of Cushing’s syndrome. Cushing’s illness is the second most prevalent cause of Cushing’s syndrome. Cushing’s disease is distinct from Cushing’s syndrome in that it refers to a single cause of the illness, a pituitary adenoma that secretes high quantities of ACTH, which raises cortisol levels.

Because cortisol enhances the vasoconstrictive impact of endogenous adrenaline, patients with Cushing’s syndrome are usually hypertensive.

Hyperglycaemia (due to insulin resistance) rather than hypoglycaemia is a common symptom.
Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater throughout the 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed.

A dexamethasone suppression test or a 24-hour urine free cortisol collection can both be used to establish the existence of Cushing’s syndrome.

Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep.

The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater throughout the 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed.

Insulin is produced by beta cells, located centrally within the islets of Langerhans, in the endocrine tissues of the pancreas. Insulin is a polypeptide hormone consisting of two short chains (A and B) linked by disulphide bonds. Proinsulin is synthesised as a single-chain peptide. Within storage granules, a connecting peptide (C peptide) is removed by proteases to yield insulin. Insulin release is stimulated initially during eating by the parasympathetic nervous system and gut hormones such as secretin, but most output is driven by the rise in plasma glucose concentration that occurs after a meal. The effects of insulin are mediated by the receptor tyrosine kinase.

Only a very small fraction of the thyroid hormones circulating in the blood are free. The majority is bound to transport proteins. Only the free thyroid hormones are biologically active, and measurement of total thyroid hormone levels can be misleading.

The relative percentages of bound and unbound thyroid hormones are:
Bound to thyroid-binding globulin -70%
Bound to albumin -15-20%
Bound to transthyretin -10-15%
Free T3 -0.3%
Free T4 -0.03%

Cushing’s syndrome is a collection of symptoms and signs caused by prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids.

The most common cause of Cushing’s syndrome is the iatrogenic administration of corticosteroids. The second most common cause of Cushing’s syndrome is Cushing’s disease.

Cushing’s disease should be distinguished from Cushing’s syndrome and refers to one specific cause of the syndrome, an adenoma of the pituitary gland that secretes large amounts of ACTH and, in turn, elevates cortisol levels. This patient has a diagnosis of Cushing’s disease, and this is, therefore, the underlying cause in this case.

The endogenous causes of Cushing’s syndrome include:
Pituitary adenoma (Cushing’s disease)
Ectopic corticotropin syndrome, e.g. small cell carcinoma of the lung
Adrenal hyperplasia
Adrenal adenoma
Adrenal carcinoma

Insulin receptor (IR), in addition to being activated by insulin, is also activated by IGF-I and IGF-II.

The IR is a dimer with two identical subunits spanning the cell membrane and are connected by a single disulphide bond. The two sub-units include: The alpha chain situated on the exterior of the cell membrane and the beta chain spanning the cell membrane in a single segment.

When insulin is detected, the alpha chains move together folding around the insulin making the beta chains move together, converting them into an active tyrosine kinase. This initiates a phosphorylation cascade increasing the expression of GLUT4 and allowing uptake of glucose by cells.

Parathyroid hormone (PTH) is a polypeptide containing 84 amino acids. It is the principal controller of free calcium in the body.
The main actions of parathyroid hormone are:
Increases plasma calcium concentration
Decreases plasma phosphate concentration
Increases osteoclastic activity (increasing calcium and phosphate resorption from bone)
Increases renal tubular reabsorption of calcium
Decreases renal phosphate reabsorption
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (via stimulation of 1-alpha hydroxylase)
Increases calcium and phosphate absorption in the small intestine (indirectly via increased 1,25-dihydroxycholecalciferol)

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

Hyperthyroidism results from an excess of circulating thyroid hormones. It is commoner in women, and incidence increases with age.

Hyperthyroidism can be subclassified into:
Primary hyperthyroidism – the thyroid gland itself is affected
Secondary hyperthyroidism – the thyroid gland is stimulated by excessive circulating thyroid-stimulating hormone (TSH).

Graves’ disease is the most common cause of hyperthyroidism (estimates are that it causes between 50 and 80% of all cases).

Although toxic multinodular goitre, thyroiditis,TSH-secreting pituitary adenoma and drug-induced hyperthyroidism also causes hyperthyroidism, the commonest cause is Graves’ disease.

The adrenal glands produce too little steroid hormones, which causes Addison’s disease. The production of glucocorticoids, mineralocorticoids, and sex steroids are all altered. The most prevalent cause is autoimmune adrenalitis, which accounts for 70-80 percent of cases.

It affects more women than males and occurs most frequently between the ages of 30 and 50.

The following are some of the clinical signs and symptoms of Addison’s disease:

Weakness and sluggishness
Hypotension is a condition in which the blood pressure (notably orthostatic hypotension)
Vomiting and nausea
Loss of weight
Axillary and pubic hair loss
Depression
Hyperpigmentation is a condition in which a person’s (palmar creases, buccal mucosa and exposed areas more commonly affected)
The following are the classic biochemical hallmarks of Addison’s disease:
Hyponatraemia
Hyperkalaemia
Hypercalcaemia
Hypoglycaemia
Acidosis metabolica
When ACTH levels are combined with cortisol levels, it is possible to distinguish between primary and secondary adrenal insufficiency:
In primary insufficiency, levels rise.
In secondary insufficiency, levels are low or low normal.

Hypocalcaemia occurs when there is abnormally low level of serum calcium ( >2.2 mmol/l) after correction for the serum albumin concentration.

Rhabdomyolysis causes hyperphosphatemia, and this leads to a reduction in ionised calcium levels.

Patients with rhabdomyolysis are commonly cared for in a high dependency care setting.

Addison’s disease, hyperthyroidism, thiazide diuretics and lithium all cause hypercalcaemia.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.

Cushing’s syndrome has a wide range of clinical manifestations that are dependent on the degree of cortisol overproduction. The appearance might be vague and the diagnosis difficult to detect when cortisol levels are just somewhat elevated. On the other hand, in long-term cases of severely increased cortisol levels, the presentation might be colourful and the diagnosis simple.

Cushing’s syndrome has the following clinical features:
Obesity and weight growth in the true sense
Supraclavicular fat pads are fat pads that are located above the clavicle.
Buffalo hump
Fullness and plethora of the face (‘moon facies’)
Muscle atrophy and weakening at the proximal level
Diabetes mellitus, also known as impaired glucose tolerance
Hypertension
Skin thinning and bruising
Depression
Hirsutism
Acne
Osteoporosis
Amenorrhoea or oligomenorrhoea

Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater during the whole 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed. As a result, random cortisol testing is not an effective screening technique and is not advised.

The following are the two most common first-line screening tests:
Cortisol levels in the urine are measured every 24 hours.
A diagnosis of Cushing’s syndrome can be made if more than two collections measure cortisol excretion more than three times the upper limit of normal.
Physical stress (e.g., excessive exercise, trauma), mental stress (e.g., sadness), alcohol or drug misuse, complex diabetes, and pregnancy can all cause false positives.
Renal dysfunction, inadequate collection, and cyclical Cushing’s disease can all cause false negatives.
The overnight low-dose dexamethasone suppression test (LDDST) involves giving 1 mg of dexamethasone at 11 p.m. and measuring blood cortisol levels at 8 a.m. the next day.
Cushing’s syndrome is diagnosed when cortisol is not suppressed to less than 50 nmol/L.
It might be difficult to tell the difference between mild Cushing’s disease and normal cortisol production.
False positives can occur as a result of depression, severe systemic sickness, renal failure, prolonged alcohol misuse, old age, and the use of hepatic enzyme-inducing medicines, among other things.
False negatives are extremely uncommon in Cushing’s disease patients.

A characteristic biochemical picture might also be helpful in confirming the diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

Osteoclasts are a type of bone cell that breaks down bone tissue. This is a critical function in the maintenance, repair and remodelling of bones. The osteoclast disassembles and digests the composite of hydrated protein and minerals at a molecular level by secreting acid and collagenase. This process is known as bone resorption and also helps to regulate the plasma calcium concentration.
Osteoclastic activity is controlled by a number of hormones:
1,25-dihydroxycholecalciferol increases osteoclastic activity
Parathyroid hormone increases osteoclastic activity
Calcitonin inhibits osteoclastic activity
Bisphosphonates are a class of drug that slow down and prevent bone damage. They are osteoclast inhibitors.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.

A typical biochemical profile can help establish a diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

​Primary hyperparathyroidism the commonest cause of hypercalcaemia. It is commonest in women aged 50 to 60.
The commonest cause of primary hyperparathyroidism is a solitary adenoma of the parathyroid gland (approximately 85% of cases).

Primary hyperparathyroidism may present with features of hypercalcaemia such as polyuria, polydipsia, renal stones, bone and joint pain, constipation, and psychiatric disorders.

In primary Hyperparathyroidism:
PTH is elevated
Calcium is elevated
Phosphate is lowered

In secondary Hyperparathyroidism:
PTH is elevated
Calcium is low or low-normal
Phosphate is raised in CRF

In tertiary Hyperparathyroidism:
PTH is elevated
Calcium is elevated
Phosphate is lowered in CRF