Congenital hypogonadotrophic hypogonadism, induction of minipuberty, and future fertility.

Summary: A 33-year-old man with Kallmann syndrome had received pulsatile GnRH as an infant for the treatment of cryptorchidism. As an adult, his treatment for fertility with gonadotrophins was unusually rapid compared with expectations, with a total sperm count of 25 million after only 12 months of gonadotrophin therapy. We propose that pulsatile GnRH treatment as an infant induced minipuberty and facilitated his successful, rapid response to therapy. We also propose that identification of the absence of minipuberty in infants with clinical signs suggesting congenital hypogonadotrophic hypogonadism (CHH) is an opportunity for intervention with pulsatile GnRH yielding benefits for fertility decades later. Learning points: Absence of minipuberty in males with CHH results in low Sertoli cell numbers and delayed response to induction of spermatogenesis in adulthood. Presentation with 'red flags' for androgen deficiency including cryptorchidism at birth, with or without micropenis, should prompt screening for CHH and minipuberty by measurement of gonadotrophins and testosterone in the first 2 months after birth. Pulsatile GnRH therapy in patients with CHH, given prior to age of attainment of Sertoli cell maturation, can replicate the normal physiology of minipuberty, thereby priming the testis for future fertility.

Aerobic Exercise Improves Microvascular Function in Older Adults.

Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease. PURPOSE: The study aimed to assess changes in peripheral microvascular function in sedentary older adults after aerobic exercise training. METHODS: Twenty-three sedentary older adults (67 ± 5 yr, body mass index = 29 ± 5, mean ± SD) successfully completed a randomized 12-wk graded treadmill walking intervention. The exercise group (EX) performed 40 min of uphill walking 4 d·wk at 70% heart rate reserve. The control group (CON) maintained a sedentary lifestyle for 12 wk. Blood oxygen level-dependent (BOLD) responses of the soleus measured by magnetic resonance imaging were used to evaluate microvascular function; brief (1 s) maximal plantarflexion contractions were performed. Separately, blood flow in the popliteal artery was measured by ultrasound after brief contraction. Phosphorus magnetic resonance spectroscopy of the calf was used to examine muscle oxidative capacity, and whole-body peak oxygen consumption (V˙O2peak) was used to confirm training-induced cardiorespiratory adaptations. RESULTS: Peak postcontraction BOLD response increased by 33% in EX (PRE, 3.3% ± 1.0%; POST, 4.4% ± 1.4%) compared with CON (PRE, 3.0% ± 1.3%; POST, 3.2% ± 1.5%), P < 0.05. EX with hypertension tended to show a blunted peak BOLD increase (n = 6, 15%) compared with EX normotensive (n = 7, 50%), P = 0.056. Peak postcontraction blood flow increased by 39% in EX (PRE, 217 ± 88 mL·min; POST, 302 ± 167 mL·min) compared with CON (PRE, 188 ± 54 mL·min; POST, 184 ± 44 mL·min), P < 0.05. EX muscle oxidative capacity (kPCr) improved by 40% (PRE, 1.60 ± 0.57 min; POST, 2.25 ± 0.80 min) compared with CON (PRE, 1.69 ± 0.28 min; POST, 1.76 ± 0.52 min), P < 0.05. V˙O2peak increased by 9% for EX (PRE, 19.0 ± 3.1 mL·kg·min; POST, 20.8 ± 2.9 mL·kg·min) compared with a 7% loss in CON (PRE, 21.9 ± 3.6 mL·kg·min; POST, 20.4 ± 3.5 mL·kg·min), P < 0.05. CONCLUSION: Moderate aerobic exercise significantly improved microvascular function of the leg in older adults.

MJA Practice Essentials--Endocrinology. 9: Pituitary disease in adults.

Pituitary adenomas are found in 10%-25% of unselected autopsy series and are evident in about 10% of asymptomatic individuals by magnetic resonance imaging. Diagnosis of pituitary disorders is often delayed by lack of awareness and the subtlety of symptoms and signs. Hypopituitarism is suspected when peripheral hormone concentrations are low without an elevation in the corresponding pituitary tropic hormone(s). Severe adult-onset growth-hormone deficiency results in reduced muscle mass, increased fat mass and diminished quality of life, which are reversed by growth hormone replacement therapy. While trans-sphenoidal surgery remains first-line treatment for acromegaly, drug treatment has an important role in controlling residual growth-hormone excess and, in some circumstances, as first-line treatment. Dopamine-agonist therapy (cabergoline or bromocriptine) is the treatment of choice for micro- and macroprolactinomas. In patients with suggestive clinical features, elevated 24-hour urine free cortisol level is usually sufficient to diagnose endogenous Cushing's syndrome; careful additional investigation is needed to determine whether the cause is Cushing's disease (pituitary adenoma secreting adrenocorticotropic hormone [ACTH]), ectopic ACTH secretion or adrenal disease. Heightened awareness is needed to detect the sometimes subtle symptoms and signs of pituitary disease