Understanding Gynaecomastia: Causes and Drug Triggers

Gynaecomastia is a condition characterized by the abnormal growth of breast tissue in males, often caused by an increased ratio of oestrogen to androgen. It is important to distinguish the causes of gynaecomastia from those of galactorrhoea, which is caused by the actions of prolactin on breast tissue.

Physiological changes during puberty can lead to gynaecomastia, but it can also be caused by syndromes with androgen deficiency such as Kallmann and Klinefelter’s, testicular failure due to mumps, liver disease, testicular cancer, and hyperthyroidism. Additionally, haemodialysis and ectopic tumour secretion can also trigger gynaecomastia.

Drug-induced gynaecomastia is also a common cause, with spironolactone being the most frequent trigger. Other drugs that can cause gynaecomastia include cimetidine, digoxin, cannabis, finasteride, GnRH agonists like goserelin and buserelin, oestrogens, and anabolic steroids. However, it is important to note that very rare drug causes of gynaecomastia include tricyclics, isoniazid, calcium channel blockers, heroin, busulfan, and methyldopa.

In summary, understanding the causes and drug triggers of gynaecomastia is crucial in diagnosing and treating this condition.

Cushing’s syndrome is the correct answer as it causes excess cortisol which can exhibit mineralocorticoid activity and lead to hypokalaemia. The kidneys play a major role in maintaining potassium balance, but other factors such as insulin, catecholamines, and aldosterone also influence potassium levels. The other options listed (congenital adrenal hypoplasia, Addison’s, rhabdomyolysis, metabolic acidosis) all cause hyperkalaemia. Addison’s disease and adrenal hypoplasia result in mineralocorticoid deficiency, leading to hyperkalaemia. Acidosis and rhabdomyolysis also cause hyperkalaemia. Symptoms of hypokalaemia include fatigue, muscle weakness, myalgia, muscle cramps, constipation, hyporeflexia, and rarely paralysis.

Causes of Cushing’s Syndrome

Cushing’s syndrome is a condition that can be caused by both endogenous and exogenous factors. However, it is important to note that exogenous causes, such as the use of glucocorticoid therapy, are more common than endogenous ones. The condition can be classified into two categories: ACTH dependent and ACTH independent causes.

ACTH dependent causes of Cushing’s syndrome include Cushing’s disease, which is caused by a pituitary tumor secreting ACTH and producing adrenal hyperplasia. Ectopic ACTH production, which is caused by small cell lung cancer, is another ACTH dependent cause. On the other hand, ACTH independent causes include iatrogenic factors such as steroid use, adrenal adenoma, adrenal carcinoma, Carney complex, and micronodular adrenal dysplasia.

In some cases, a condition called Pseudo-Cushing’s can mimic Cushing’s syndrome. This is often caused by alcohol excess or severe depression and can cause false positive results in dexamethasone suppression tests or 24-hour urinary free cortisol tests. To differentiate between Cushing’s syndrome and Pseudo-Cushing’s, an insulin stress test may be used.

The insertion of aquaporin-2 channels is promoted by antidiuretic hormone, which facilitates water reabsorption. However, in the case of syndrome of inappropriate antidiuretic hormone secretion (SiADH), which is caused by small cell lung cancer, the normal negative feedback loop fails, resulting in the continuous production of ADH even when serum osmolality returns to normal. This leads to euvolemic hyponatremia, where the body retains water but continues to lose sodium, resulting in concentrated urine. The underlying mechanism of this condition is the persistent increase in the number of aquaporin-2 channels, which promotes water reabsorption, rather than any effect on sodium transport mechanisms.

Understanding Antidiuretic Hormone (ADH)

Antidiuretic hormone (ADH) is a hormone that is produced in the supraoptic nuclei of the hypothalamus and released by the posterior pituitary gland. Its primary function is to conserve body water by promoting water reabsorption in the collecting ducts of the kidneys through the insertion of aquaporin-2 channels.

ADH secretion is regulated by various factors. An increase in extracellular fluid osmolality, a decrease in volume or pressure, and the presence of angiotensin II can all increase ADH secretion. Conversely, a decrease in extracellular fluid osmolality, an increase in volume, a decrease in temperature, or the absence of ADH can decrease its secretion.

Diabetes insipidus (DI) is a condition that occurs when there is either a deficiency of ADH (cranial DI) or an insensitivity to ADH (nephrogenic DI). Cranial DI can be treated with desmopressin, which is an analog of ADH.

Overall, understanding the role of ADH in regulating water balance in the body is crucial for maintaining proper hydration and preventing conditions like DI.

DPP-4 inhibitors, also known as gliptins, function by decreasing the breakdown of incretins like GLP-1 in the periphery. This leads to an increase in incretin levels, which in turn lowers blood glucose levels.

It is important to note that increasing the peripheral breakdown of incretin would have the opposite effect and worsen glycaemic control.

Metformin, on the other hand, works by enhancing the uptake of insulin in the periphery.

Reducing the secretion of insulin from the pancreas would not be an effective mechanism and would actually raise glucose levels in the blood.

SGLT2 inhibitors, such as dapagliflozin, function by reducing the reabsorption of glucose in the kidneys.

Diabetes mellitus is a condition that has seen the development of several drugs in recent years. One hormone that has been the focus of much research is glucagon-like peptide-1 (GLP-1), which is released by the small intestine in response to an oral glucose load. In type 2 diabetes mellitus (T2DM), insulin resistance and insufficient B-cell compensation occur, and the incretin effect, which is largely mediated by GLP-1, is decreased. GLP-1 mimetics, such as exenatide and liraglutide, increase insulin secretion and inhibit glucagon secretion, resulting in weight loss, unlike other medications. They are sometimes used in combination with insulin in T2DM to minimize weight gain. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as vildagliptin and sitagliptin, increase levels of incretins by decreasing their peripheral breakdown, are taken orally, and do not cause weight gain. Nausea and vomiting are the major adverse effects of GLP-1 mimetics, and the Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that it has been linked to severe pancreatitis in some patients. NICE guidelines suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated, or the person has had a poor response to a thiazolidinedione.

Understanding Prolactin and Galactorrhoea

Prolactin is a hormone produced by the anterior pituitary gland, and its release is regulated by various physiological factors. Dopamine is the primary inhibitor of prolactin release, and dopamine agonists like bromocriptine can be used to manage galactorrhoea. It is crucial to distinguish between the causes of galactorrhoea and gynaecomastia, which are both related to the actions of prolactin on breast tissue.

Excess prolactin can lead to different symptoms in men and women. Men may experience impotence, loss of libido, and galactorrhoea, while women may have amenorrhoea and galactorrhoea. Several factors can cause raised prolactin levels, including prolactinoma, pregnancy, oestrogens, stress, exercise, sleep, acromegaly, polycystic ovarian syndrome, and primary hypothyroidism.

Certain drugs can also increase prolactin levels, such as metoclopramide, domperidone, phenothiazines, and haloperidol. Although rare, some SSRIs and opioids may also cause raised prolactin levels.

In summary, understanding prolactin and its effects on the body is crucial in diagnosing and managing conditions like galactorrhoea. Identifying the underlying causes of raised prolactin levels is essential in providing appropriate treatment and care.

The correct answer is Addison’s disease, which is a condition of primary adrenal insufficiency. One of the hormones that is deficient in this disease is aldosterone, which plays a crucial role in maintaining the balance of potassium in the body. Aldosterone activates Na+/K+ ATPase pumps on the cell wall, causing the movement of potassium into the cell and increasing renal potassium secretion. Therefore, a lack of aldosterone leads to hyperkalaemia.

Phaeochromocytomas are tumours that produce catecholamines and typically arise in the adrenal medulla. They are associated with hypertension and hyperglycaemia, but not disturbances in potassium balance.

Hyperthyroidism is a condition of excess thyroid hormone and does not affect potassium balance.

Conn’s syndrome, on the other hand, is a type of primary hyperaldosteronism where there is excess aldosterone production. Aldosterone activates the Na+/K+ pump on the cell wall, causing the movement of potassium into the cell, which can lead to hypokalaemia.

Addison’s disease is the most common cause of primary hypoadrenalism in the UK, with autoimmune destruction of the adrenal glands being the main culprit, accounting for 80% of cases. This results in reduced production of cortisol and aldosterone. Symptoms of Addison’s disease include lethargy, weakness, anorexia, nausea and vomiting, weight loss, and salt-craving. Hyperpigmentation, especially in palmar creases, vitiligo, loss of pubic hair in women, hypotension, hypoglycemia, and hyponatremia and hyperkalemia may also be observed. In severe cases, a crisis may occur, leading to collapse, shock, and pyrexia.

Other primary causes of hypoadrenalism include tuberculosis, metastases (such as bronchial carcinoma), meningococcal septicaemia (Waterhouse-Friderichsen syndrome), HIV, and antiphospholipid syndrome. Secondary causes include pituitary disorders, such as tumours, irradiation, and infiltration. Exogenous glucocorticoid therapy can also lead to hypoadrenalism.

It is important to note that primary Addison’s disease is associated with hyperpigmentation, while secondary adrenal insufficiency is not.

Calcitonin is used in clinical practice to detect recurrence of medullary thyroid cancer. Thyroid function tests are not used for diagnosis or follow-up of malignancies. However, regular monitoring of TSH levels may be necessary for patients taking thyroxine.

Thyroid cancer rarely causes hyperthyroidism or hypothyroidism as it does not usually secrete thyroid hormones. The most common type of thyroid cancer is papillary carcinoma, which is often found in young females and has an excellent prognosis. Follicular carcinoma is less common, while medullary carcinoma is a cancer of the parafollicular cells that secrete calcitonin and is associated with multiple endocrine neoplasia type 2. Anaplastic carcinoma is rare and not responsive to treatment, causing pressure symptoms. Lymphoma is also rare and associated with Hashimoto’s thyroiditis.

Management of papillary and follicular cancer involves a total thyroidectomy followed by radioiodine to kill residual cells. Yearly thyroglobulin levels are monitored to detect early recurrent disease. Papillary carcinoma usually contains a mixture of papillary and colloid filled follicles, while follicular adenoma presents as a solitary thyroid nodule and malignancy can only be excluded on formal histological assessment. Follicular carcinoma may appear macroscopically encapsulated, but microscopically capsular invasion is seen. Medullary carcinoma is associated with raised serum calcitonin levels and familial genetic disease in up to 20% of cases. Anaplastic carcinoma is most common in elderly females and is treated by resection where possible, with palliation achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.

The patient’s symptoms and history suggest a diagnosis of hypothyroidism, which is commonly caused by Hashimoto’s thyroiditis in developed countries. This autoimmune condition is more prevalent in women and certain populations, such as the elderly and those with HLA-DR3, 4, and 5 polymorphisms. Other thyroid conditions, such as subacute thyroiditis, Riedel’s thyroiditis, multinodular goitres, and papillary carcinoma, have different characteristic features.

Understanding Hashimoto’s Thyroiditis

Hashimoto’s thyroiditis is a chronic autoimmune disorder that affects the thyroid gland. It is more common in women and is typically associated with hypothyroidism, although there may be a temporary period of thyrotoxicosis during the acute phase. The condition is characterized by a firm, non-tender goitre and the presence of anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) antibodies.

Hashimoto’s thyroiditis is often associated with other autoimmune conditions such as coeliac disease, type 1 diabetes mellitus, and vitiligo. Additionally, there is an increased risk of developing MALT lymphoma with this condition. It is important to note that many causes of hypothyroidism may have an initial thyrotoxic phase, as shown in the Venn diagram. Understanding the features and associations of Hashimoto’s thyroiditis can aid in its diagnosis and management.

Diabetes mellitus is a condition that has seen the development of several drugs in recent years. One hormone that has been the focus of much research is glucagon-like peptide-1 (GLP-1), which is released by the small intestine in response to an oral glucose load. In type 2 diabetes mellitus (T2DM), insulin resistance and insufficient B-cell compensation occur, and the incretin effect, which is largely mediated by GLP-1, is decreased. GLP-1 mimetics, such as exenatide and liraglutide, increase insulin secretion and inhibit glucagon secretion, resulting in weight loss, unlike other medications. They are sometimes used in combination with insulin in T2DM to minimize weight gain. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as vildagliptin and sitagliptin, increase levels of incretins by decreasing their peripheral breakdown, are taken orally, and do not cause weight gain. Nausea and vomiting are the major adverse effects of GLP-1 mimetics, and the Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that it has been linked to severe pancreatitis in some patients. NICE guidelines suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated, or the person has had a poor response to a thiazolidinedione.

Long-term use of steroids can lead to a higher risk of psychiatric disorders such as depression, mania, psychosis, and insomnia. This risk is even greater if the patient has a history of recreational drug use or mental disorders. While proximal myopathy is a known adverse effect of long-term steroid use, distal myopathy is not commonly observed. However, some studies have reported it as a rare and uncommon adverse effect. Steroids are also known to increase appetite, leading to weight gain, making the last two options incorrect.

Corticosteroids are commonly prescribed medications that can be taken orally or intravenously, or applied topically. They mimic the effects of natural steroids in the body and can be used to replace or supplement them. However, the use of corticosteroids is limited by their numerous side effects, which are more common with prolonged and systemic use. These side effects can affect various systems in the body, including the endocrine, musculoskeletal, gastrointestinal, ophthalmic, and psychiatric systems. Some of the most common side effects include impaired glucose regulation, weight gain, osteoporosis, and increased susceptibility to infections. Patients on long-term corticosteroids should have their doses adjusted during intercurrent illness, and the medication should not be abruptly withdrawn to avoid an Addisonian crisis. Gradual withdrawal is recommended for patients who have received high doses or prolonged treatment.