Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .

/pdf/protective-and-damaging-effects-of-stress-mediators-34e0m747fy.pdf

Protective and Damaging Effects of Stress Mediators

Objective: The aim was to formulate practice guidelines for endocrine treatment oftranssexual persons. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. Consensus Process: Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. Conclusions: Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person’s genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person’s desired gender. A mental health professional ...

/pdf/endocrine-treatment-of-transsexual-persons-an-endocrine-2qlptvdf9y.pdf

Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline

Hormonal correlates of paternal responsiveness in new and expectant fathers

An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or...

https://www.nejm.org/doi/pdf/10.1056/NEJM197703172961103?listPDF=true

Galactorrhea: A Study of 235 Cases, Including 48 with Pituitary Tumors

To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.

Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. Pathophysiologic mechanisms in underweight and weight-corrected patients.

We studied cortisol secretion and metabolism in 10 women with anorexia nervosa. The 24-hour mean plasma cortisol concentration was 8.9 mug per deciliter (controls, 4.9) (P less than 0.01). Secretory patterns showed normal circadian rhythms. Cortisol half-life was prolonged from 60 to 78 minutes (P less than 0.01), and metabolic clearance rate was decreased from 359 to 177 liters per day (P less than 0.001). Cortisol production was normal (19.4 mg per day). Urinary cortisol was slightly elevated in two of five patients. These findings, as well as the increased tetrahydrocortisol/tetrahydrocortisone ratio (1.2 vs 0.65, P less than 0.01), also appear in hypothyroid patients. Thyroid-function studies showed normal total and free thyroxine and thyrotropin, but low plasma tri-iodothyronine levels (52.7+/-13.2 vs. 137.8+/-24.1 ng per deciliter in the controls, P less than 0.001). In five additional patients with anorexia nervosa studied before and after short-term tri-iodothyronine administration, metabolic abnormalities decreased as plasma tri-iodothyronine levels rose to or above normal.

Cortisol Secretion and Metabolism in Anorexia Nervosa

Prolactin secretion in normal adults is characterized by periods of episodic secretion which increase in magnitude during sleep. In this study, we report the 24-h mean prolactin concentrations, prolactin secretory patterns, and associated pituitary hormone function in nine patients (seven women and two men) with hyperprolactinemia of diverse etiologies. Four of the women and one of the men had clinically demonstrable pituitary tumors, one boy had a hypothalamic tumor, and the three other women had "functional" hyperprolactinemia. The 24-h mean prolactin concentrations derived from averaging the 20-min interval samples for 24 h ranged from 28.6 to 1,220 ng/ml. The plasma prolactin patterns in these patients showed persistence of episodic secretion in all and loss of the normal sleep-wake difference in plasma prolactin in seven of nine. Three of the patients with galactorrhea and comparable 24-h mean prolactin concentrations (58.3, 59.7, and 64.3 ng/ml) showed similar prolactin secretory patterns despite different etiologic mechanisms. Evaluation of the secretory patterns of luteinizing hormone (LH) in these patients showed loss of normal pulsatile LH release and a low 24-h mean LH concentration in the patient with the pituitary tumor, while the two patients without clinically demonstrable pituitary tumors ("post-pill" galactorrhea and "idiopathic" galactorrhea) showed normal LH secretory patterns and 24-h mean LH concentrations. The 24-h mean cortisol concentrations and secretory patterns were normal in five of the seven patients who had these parameters measured. The patient with the hypothalamic tumor had a low 24-h mean cortisol concentration and production rate and absent response to metyrapone. The patient with "idiopathic" galactorrhea had an elevated 24-h mean cortisol concentration but normal cortisol production rate and urinary 17-hydroxycorticoid excretion. Growth hormone secretion was abnormal in four of the patients (one with the hypothalamic tumor and three with pituitary tumors). Thyrotropin-releasing hormone (TRH) administration in four patients resulted in normal TSH release in two patients (one of whom developed galactorrhea after the test), an absent response in the patient with the hypothalamic tumor, and a blunted response in one of the women with a pituitary tumor. The two men had low 24-h mean plasma testosterone concentrations (69 and 30 ng/100 ml) and symptoms of impotence and loss of libido. Five of the women (four with pituitary tumors and one with Chiari-Frommel syndrome) had either low 24-h mean LH concentrations, abnormal LH secretory patterns, or both. These data indicate that patients with hyperprolactinemia encompassing a varied etiological range frequently show loss of the normal sleep-associated increase in prolactin secretion as well as abnormalities in the regulation of the other hypothalamic pituitary-regulated hormones. The finding that the abnormalities in LH, growth hormone, thyrotropin, and cortisol (adrenocorticotrophic) secretion were almost uniformly confined to the patients with the clinically demonstrable hypothalamic or pituitary tumors suggests that the size of the lesion is the critical factor.

/pdf/hypothalamic-pituitary-function-in-diverse-qcmi4389gs.pdf

Hypothalamic-Pituitary Function in Diverse Hyperprolactinemic States

Plasma luteinizing hormone, follicle-stimulating hormone, and estradiol were measured at 20-minute intervals for 24-hours in seven pubertal premenarchal girls whose sleep was monitored polygraphically. A circadian variation in plasma estradiol was demonstrated with the highest values occurring during the day (1400-1600 hours) and lowest values during sleep, a time when gonadotropin secretion was augmented.

Human puberty: 24-hour estradiol patterns in pubertal girls

To determine if the central nervous system “program” controlling PRL secretion is operative during pregnancy, three pregnant women (12th, 20th and 32nd week of gestation) had 24-hour, 20-minute interval plasma sampling and polygraphic monitoring of nocturnal sleep. All three subjects showed episodic PRL secretion during waking which became augmented during nocturnal sleep. Since the number f“major” PRL secretory episodes was similar to normals, the increased PRL levels were most probably achieved by increased secretion per secretory episode. These findings suggest that during pregnancy, the PRL sleep related secretory “program” is maintained in a qualitative manner, albeit at a higher set-point.

Twenty-four hour prolactin (prl) secretory patterns during pregnancy.

Plasma luteinizing hormone (LH) was measured by radioimmunoassay at 20-min intervals for 24-hr in 5 normal men before and after the daily administration of 100 mg clomiphene citrate for 7 days. The results showed that clomiphene caused a significant (P < 0.001) increase in the 24-hr mean LH concentration in all 5 subjects. The range of the percent increase was 135–245 with a mean of 180%. In spite of the highly significant increase in the 24-hr mean LH concentration there were instances of overlap of isolated LH values in the control and clomiphene studies. Analysis of the 24-hr plasma curves showed that the increased mean LH concentration was achieved by either increasing the amount of LH secreted per secretory episode or the number of major secretory episodes or both. Calculation of the LH production rate from the 24-hr LH secretory patterns showed a mean percent increase of 189% with a range of 149–259. Estimation of the LH “half-life” from the declining phase of the secretory episodes showed a cluster...

R. M. Boyar

Papers

Cortisol Secretion and Metabolism in Anorexia Nervosa

Hypothalamic-Pituitary Function in Diverse Hyperprolactinemic States

Human puberty: 24-hour estradiol patterns in pubertal girls

Twenty-four hour prolactin (prl) secretory patterns during pregnancy.

The Effect of Clomiphene Citrate on the 24-Hour LH Secretory Pattern in Normal Men