Pathophysiology
Summary
Endocrine pathology encompasses a wide array of disorders that impact the hypothalamic-pituitary-adrenal axis, gonads, and other hormone-secreting organs like the adrenals. A fundamental grasp of the physiological interactions among these organs is essential for diagnosis and management of conditions like hypogonadism, adrenal insufficiency, and hypothyroidism.
Hypogonadism originates from either the gonads (primary) or the pituitary gland (secondary). In primary hypogonadism, increased secretion of gonadotropin-releasing hormone (GnRH) leads to elevated LH & FSH due to the decreased negative feedback from the gonads. In contrast, secondary hypogonadism, often the first sign of a pituitary adenoma, shows decreased LH & FSH levels. Hypogonadism presents with estrogen deficiency and menopausal symptoms in women, testosterone deficiency in men, and delayed puberty in children.
In adrenal insufficiency, dysfunction can arise either directly from the adrenal glands (primary) or due to pituitary gland issues (secondary). Secondary adrenal insufficiency shows reduced ACTH and cortisol levels, but mineralocorticoid production remains intact. Symptoms include weakness, hypoglycemia, and the risk of progression to adrenal crisis.
The metyrapone test and cosyntropin stimulation test can help differentiate between primary and secondary adrenal insufficiency. Metyrapone inhibits 11β-hydroxylase, reducing cortisol and elevating ACTH in a healthy HPA axis, but not in cases of anterior pituitary dysfunction. Cosyntropin, a synthetic ACTH, triggers cortisol release from the adrenal glands, except in primary adrenal insufficiency.
Hypothyroidism is usually primary (due to dysfunction of the thyroid gland), but can be secondary (pituitary dysfunction) or tertiary (hypothalamic dysfunction). In secondary hypothyroidism, both TSH and thyroid hormone levels are low. Clinical symptoms may include weight gain, cold intolerance, bradycardia, constipation, and slow deep tendon reflexes.
Growth hormone (GH) deficiency is often due to dysfunction in the anterior pituitary and results in low levels of insulin-like growth factor 1 (IGF-1). In children, it manifests as growth failure, delayed bone age, and other physical anomalies. In adults, symptoms include muscle wasting and truncal obesity.
Injury to the pituitary stalk or hypothalamic dysfunction can lead to increased levels of prolactin due to reduced dopamine inhibition. Additionally, hypothalamic dysfunction can affect oxytocin & ADH release from the posterior pituitary, leading to issues like impaired uterine contractions during childbirth (oxytocin) and diabetes insipidus (ADH)
Lesson Outline
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FAQs
Primary hypogonadism is caused when the gonads (ovaries or testicles) are dysfunctional, leading to a deficiency in the production of crucial hormones like estrogen or testosterone. This dysfunction prompts an increase in the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary, due to a lack of negative feedback from the deficient gonadal hormones. On the other hand, secondary hypogonadism is caused by a dysfunction in the pituitary gland. Despite an increase in GnRH due to a lack of feedback from gonadal hormones, LH and FSH secretion is decreased due to the pituitary dysfunction. Consequently, gonadal hormone levels decrease, due to lack of stimulation by LH and FSH.
Adrenal insufficiency, particularly secondary adrenal insufficiency, and hypogonadism can both result from hypothalamic and pituitary dysfunction. With the pituitary gland not functioning correctly, its unable to efficiently signal the adrenal gland to produce enough cortisol, leading to adrenal insufficiency. Meanwhile, the hypothalamus struggles to produce enough GnRH to trigger the pituitary gland to release crucial reproductive hormones like LH and FSH, leading to hypogonadism.
The hypothalamus regulates pituitary hormone production by producing and secreting releasing hormones. These releasing hormones stimulate the anterior pituitary to secrete its own hormones. Two important examples are the secretion of GnRH which stimulates the secretion of LH and FSH from the pituitary, and the hypothalamic secretion of corticotropin-releasing hormone (CRH) that triggers the secretion of ACTH from the pituitary.
Various manifestations may indicate potential hypothalamic and pituitary dysfunction. For instance, primary hypogonadism could lead to amenorrhea, infertility, vaginal atrophy, hot flashes, decreased breast tissue, and decreased bone mineral density in women or impotence and infertility in men due to estrogen or testosterone deficiency, respectively. Similarly, adrenal insufficiency can present as weakness, fatigue, muscle pain, and hypoglycemia, among other symptoms. Hypothyroidism could present with symptoms like weight gain, cold intolerance, bradycardia, and constipation. Each disorder yields its unique set of clinical manifestations which help in their identification.
Growth Hormone (GH) deficiency can present different symptoms in children and adults. In children, growth failure, immature face, infantile "cherub-like" fat distribution, decreased hair growth, small genitalia, delayed puberty, and delayed bone age could be indicators of GH deficiency. In contrast, in adults, symptoms might include muscle wasting, truncal obesity, decreased bone density, and osteoporosis. Levels of insulin-like growth factor 1 (IGF-1) are typically low in those with GH deficiency too. It's important to consult with a healthcare professional who can conduct further testing and make a diagnosis.
