Can this problem be caused by any hormonal disturbance?

Can Hormonal Disturbances Cause This Problem?

Yes, numerous hormonal disturbances can cause a wide range of clinical problems, particularly affecting reproductive function, growth, metabolism, and overall health.

Reproductive and Menstrual Disorders

Hormonal disturbances are a primary cause of reproductive dysfunction, particularly in women:

• Menstrual irregularities (oligomenorrhea, amenorrhea, polymenorrhea) are frequently caused by hormonal imbalances including polycystic ovary syndrome (PCOS), hypothalamic amenorrhea, hyperprolactinemia, and thyroid dysfunction 1.

• Primary amenorrhea can result from hypogonadotropic hypogonadism (low FSH/LH with low estradiol) or hypergonadotropic hypogonadism (elevated FSH/LH with low estradiol), requiring measurement of serum FSH and LH levels to differentiate 2.

• Secondary amenorrhea affects 3-4% of women and is commonly caused by functional hypothalamic amenorrhea (20-35% of cases), PCOS, hyperprolactinemia (20% of cases), and primary ovarian insufficiency 3.

• Infertility requires endocrinology and/or gynecology consultation to exclude PCOS, hypothalamic amenorrhea, hyperprolactinemia, and thyroid dysfunction 1.

Specific Hormonal Disorders to Evaluate

Thyroid Dysfunction

• Both hypothyroidism and hyperthyroidism can cause menstrual irregularities and amenorrhea 3.
• Thyroid hormone levels (TSH and free T3) should be measured when evaluating reproductive dysfunction 1.
• Hypothyroidism can cause growth failure in children independent of other conditions 1.

Hyperprolactinemia

• Accounts for approximately 20% of secondary amenorrhea cases 3.
• Morning resting serum prolactin levels >20 μg/L are abnormal (avoid postictal measurements) 1.
• May indicate pituitary tumors or be drug-induced; requires ruling out hypothyroidism 1.
• Clinical features include galactorrhea (crusting on nipples, breast milk expression in non-lactating women) 1.

Polycystic Ovary Syndrome (PCOS)

• One of the most common causes of secondary amenorrhea 3.
• Characterized by elevated testosterone (>2.5 nmol/L), LH/FSH ratio >2, and polycystic ovarian morphology on ultrasound 1.
• Serum AMH >60 pmol/L increases odds of menstrual disturbance 28.5-fold compared to AMH <15 pmol/L 4.
• Associated with obesity, hirsutism, and insulin resistance 1.

Hypogonadism

• In men: Presents with reduced libido, erectile dysfunction, decreased spontaneous erections, decreased energy, and reduced physical strength 1.
• In women: Low estrogen states (functional hypothalamic amenorrhea) cause decreased estradiol and progesterone, not excess estrogen 3.
• Can be primary (testicular/ovarian failure) or secondary (hypothalamic-pituitary dysfunction) 1, 2.

Growth Hormone Disturbances

• GH insensitivity is the main hormonal disturbance causing growth failure in chronic kidney disease 1.
• Pubertal delay results from reduced GnRH release and decreased bioactive LH levels 1.
• Hypothyroidism and GH deficiency cause growth failure independent of underlying conditions 1.

Endocrinopathies from Immune Checkpoint Inhibitors

• Median time to onset is 14.5 weeks (range 1.5-130 weeks) 1.
• Can affect any endocrine organ including pituitary, thyroid, adrenal, and pancreas 1.
• Requires distinguishing primary from secondary hormonal problems to ensure appropriate treatment 1.

Diagnostic Approach

Initial evaluation should include:

• Pregnancy test as the first step 3.
• Serum FSH, LH, prolactin, and TSH levels 3.
• Testosterone measurement (day 3-6 of cycle in women) 1.
• Progesterone during mid-luteal phase (<6 nmol/L indicates anovulation) 1.
• Morning cortisol with simultaneous ACTH to distinguish primary from secondary adrenal insufficiency 1.

Imaging studies when indicated:

• Transvaginal pelvic ultrasound is more sensitive than transabdominal for identifying ovarian pathology, including >10 peripheral cysts (2-8 mm diameter) suggesting PCOS 1.
• Pituitary MRI when galactorrhea or hyperprolactinemia suggests hypothalamic-pituitary axis abnormality 1.

Critical Clinical Pitfalls

• Never replace thyroid hormone before cortisol in patients with multiple pituitary hormone deficiencies, as this can trigger adrenal crisis 1.
• Avoid measuring prolactin post-seizure as it will be falsely elevated 1.
• Do not measure IGFBP3 in CKD patients as low-molecular-mass fragments accumulate and cause falsely elevated results 1.
• Distinguish central from primary hypothyroidism by measuring both TSH and free T4, as low TSH may indicate either hyperthyroidism or central hypothyroidism 1.
• Evaluate for adrenal insufficiency before initiating thyroid hormone replacement to prevent acute adrenal crisis 1, 5.