Functional hypothalamic amenorrhea: case presentations and overview of literature.

Functional hypothalamic amenorrhea is a form of chronic anovulation not due to identifiable organic causes with adverse health consequences. A thorough history is paramount in the identification of women with this disorder as it is usually associated with lifestyle factors such as stress, weight loss, and excessive exercise. In this paper, recently published clinical guidelines are reviewed and a series of cases is presented that highlights diagnostic and therapeutic challenges encountered.

Glycemic Control and Bone Turnover in Older Mexican Americans with Type 2 Diabetes.

Altered bone quality, caused by underlying metabolic changes of type 2 diabetes (T2D), has been hypothesized to cause altered bone strength and turnover leading to increased fracture risk in T2D patients. Current understanding about changes in bone turnover markers in T2D patients is mainly based on studies focused on Caucasian men and women. However, Hispanic populations have the highest prevalence of both T2D and osteoporosis in the US. We investigated associations of glycemic control (in terms of glycated hemoglobin [HbA1c]) and bone turnover rate in 69 older (≥50 years) Mexican American Cameron County Hispanic Cohort (CCHC) participants with T2D. Multivariable analyses were conducted to assess the associations between HbA1c (%), serum osteocalcin (OC), and serum sclerostin. In agreement with published reports from other racial/ethnic populations, our study found that lower bone turnover (indicated by lower serum OC) occurred in Mexican American men with T2D who had poorer glycemic control. For the women in our study, we found no significant association between glycemic control and OC. In contrast, HbA1c was positively associated with sclerostin for women, with near significance (p = 0.07), while no association was found in men. We recommend screening Mexican American individuals with T2D, specifically those with poor glycemic control, for bone loss and fracture risk.

Lumbar Spine Trabecular Bone Score (TBS) Reflects Diminished Bone Quality in Patients With Diabetes Mellitus and Oral Glucocorticoid Therapy.

Trabecular bone score (TBS) is a texture parameter that measures the grayscale variation within dual-energy X-ray absorptiometry (DXA) images, and has been shown to significantly correlate with the 3-dimensional bone microarchitecture. The objective of this study was to determine whether TBS is a better clinical tool than traditionally used bone mineral density (BMD) to detect the skeletal deterioration seen in patients with diabetes (DM), patients undergoing oral glucocorticoid (GC) therapy, and patients who are both diabetic and taking steroids (GC + DM). We performed retrospective, cross-sectional study using DXA images of patients who visited UTHealth Department of Internal Medicine DXA clinic in Houston, TX, from May 30, 2014 to May 30, 2016. A total of 477 men and women, who were 55 years or older, were included in the study. Lumbar spine (LS) BMD and TBS were collected. Electronic medical records were reviewed to collect clinical information for each patient. When both men and women were analyzed as a single group, LS-BMD was significantly higher in the diabetic group than in the control group (1.14 vs 1.10, p = 0.038), whereas mean TBS of L1-L4 was significantly lower in the diabetic group (1.21 vs 1.26, p = 0.004). LS-TBS was also significantly lower in diabetic women than in nondiabetic women (1.20 vs 1.26, p = 0.002). Receiver operating characteristic curves and areas under the curve indicated that LS-TBS provided better ability than LS-BMD to discriminate between control subjects and those in the DM, GC, or GC + DM groups (areas under the curve between 0.645 and 0.697, p < 0.010 for all). LS-TBS is a BMD-independent parameter that is capable of capturing a larger portion of bone quality deterioration undetected by BMD alone in patients with DM and undergoing oral GC therapy.

MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview.

Aging and its underlying pathophysiological background has always attracted the attention of the scientific society. Defined as the gradual, time-dependent, heterogeneous decline of physiological functions, aging is orchestrated by a plethora of molecular mechanisms, which vividly interact to alter body homeostasis. The ability of an organism to adjust to these alterations, in conjunction with the dynamic effect of various environmental stimuli across lifespan, promotes longevity, frailty or disease. Endocrine function undergoes major changes during aging, as well. Specifically, alterations in hormonal networks and concomitant hormonal deficits/excess, augmented by poor sensitivity of tissues to their action, take place. As hypothalamic-pituitary unit is the central regulator of crucial body functions, these alterations can be translated in significant clinical sequelae that can impair the quality of life and promote frailty and disease. Delineating the hormonal signaling alterations that occur across lifespan and exploring possible remedial interventions could possibly help us improve the quality of life of the elderly and promote longevity.

Hyperandrogenism during puberty in the development of polycystic ovary syndrome.

The hormonal events of puberty, from adrenarche to menarche and beyond, include the secretion of androgens as well as estrogen and P. This normal pubertal process is briefly reviewed and a physiologic role for pubertal androgens proposed. It is further suggested that the hyperandrogenic state we call polycystic ovary syndrome is a maladaptation of the advantageous role of normal pubertal androgens.

Self-reported reproductive health in women with tuberous sclerosis complex.

PURPOSE: Little is known about sex-specific manifestations of tuberous sclerosis complex. Inactivating mutations in the TSC1 and TSC2 genes cause tuberous sclerosis complex, and recent evidence points to a crucial role for these genes in maintaining appropriate ovarian function. The main objective of this study was to estimate reproductive dysfunction in a sample of women with tuberous sclerosis complex. METHODS: We designed a three-part questionnaire that included demographic information, reproductive history, and tuberous sclerosis complex history, and developed strict criteria to assess patterns in menstrual cyclicity; we analyzed 182 responses from female adult members of the Tuberous Sclerosis Alliance. RESULTS: More than one-third of women in our sample displayed some degree of menstrual irregularity, and their reported miscarriage rate was 41%. More than 4% of women had reproductive histories suggestive of premature ovarian insufficiency, higher than the general population estimate of 1%. CONCLUSION: Our data reveal an underappreciated aspect of tuberous sclerosis complex in affected women, suggesting that a further exploration of the role the tuberous sclerosis complex genes play in reproductive function is warranted.

GnRH-deficient phenotypes in humans and mice with heterozygous variants in KISS1/Kiss1.

CONTEXT: KISS1 is a candidate gene for GnRH deficiency. OBJECTIVE: Our objective was to identify deleterious mutations in KISS1. PATIENTS AND METHODS: DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions. RESULTS: Fifteen probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control subjects. Of the variants that reside within the mature kisspeptin peptide, p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate generation. Of the variants that lie within the coding region but outside the mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be deleterious. Of the variants that lie outside the coding region, one (g.1-3659C→T) impairs transcription in vitro, and another (c.1-7C→T) lies within the consensus Kozak sequence. Of five probands tested, four had abnormal baseline LH pulse patterns. In mice, testosterone decreases with heterozygous loss of Kiss1 and Kiss1r alleles (wild-type, 274 ± 99, to double heterozygotes, 69 ± 16 ng/dl; r(2) = 0.13; P = 0.03). Kiss1/Kiss1r double-heterozygote males have shorter anogenital distances (13.0 ± 0.2 vs. 15.6 ± 0.2 mm at P34, P < 0.001), females have longer estrous cycles (7.4 ± 0.2 vs. 5.6 ± 0.2 d, P < 0.01), and mating pairs have decreased litter frequency (0.59 ± 0.09 vs. 0.71 ± 0.06 litters/month, P < 0.04) and size (3.5 ± 0.2 vs. 5.4 ± 0.3 pups/litter, P < 0.001) compared with wild-type mice. CONCLUSIONS: Deleterious, heterozygous RSV in KISS1 exist at a low frequency in GnRH-deficient patients as well as in the general population in presumably normal individuals. As in Kiss1(+/-)/Kiss1r(+/-) mice, heterozygous KISS1 variants in humans may work with other genetic and/or environmental factors to cause abnormal reproductive function.

Antithyroid peroxidase antibodies in patients with high normal range thyroid stimulating hormone.

BACKGROUND AND OBJECTIVES: Hypothyroidism is linked to heart disease and decreased quality of life. Since screening guidelines for the general population are controversial, and physicians use clinical judgment in deciding to order thyroid stimulating hormone (TSH), high-normal levels of TSH pose a dilemma. This study's objective was to compare rates of positive anti-thyroid peroxidase antibodies (antiTPO) tests in persons with high-normal versus low-normal TSH levels. METHODS: Physicians at a publicly funded family medicine outpatient clinic used a standard clinical set of criteria to identify patients in need of TSH testing. Patients with non-thyroid diseases or conditions that affect TSH were excluded. A total of 143 patients over 18 years of age presented with symptoms necessitating TSH testing and had levels that fell between 0.36 and 5.49 IU/ml. They were allocated into two groups: 100 patients with TSH levels between 0.36--2.49 IU/ml (low-normal TSH ) and 43 patients with TSH levels between 2.5--5.49 IU/ml (high-normal TSH ), and they all had measurements of antiTPO levels. Primary outcomes were rates of antiTPO and demographics comparisons between the two groups. RESULTS: The prevalence of the antiTPO antibody in the high-normal group was 18.6% versus 3% in the low-normal range TSH. The antiTPO prevalence was higher in females than in males and had a racial predominance in Hispanics compared to African Americans; however, these differences were not statistically significant. CONCLUSIONS: AntiTPO measurement may be appropriate for patients with high-normal TSH to help distinguish those at risk of developing true hypothyroidism.

Reproductive endocrinology: live birth prediction in polycystic ovary syndrome.

Anovulatory infertility is common in polycystic ovary syndrome (PCOS). Clinicians who provide first-line treatment have to decide how best to induce ovulation with the desired outcome of live birth, a decision often complicated by the phenotypic heterogeneity of PCOS. could a new livebirth prediction model of different ovulation induction methods developed from basic clinical parameters help select infertility treatments?

Treatment for polycystic ovary syndrome: a critical appraisal of treatment options.

The management of polycystic ovary syndrome (PCOS) usually spans a woman's reproductive years. While the treatment of symptoms is a primary concern, given its long-term nature, the benefits and potential risks need to be assessed and balanced. The variability of presentation coupled with the phenotypic diversity of this patient population, requires the individualization of treatment to each patient. Periodically, the regimen has to be modified owing to a desire for pregnancy, necessitating ovulation induction in this anovulatory group of women. Finally, for any treatment offered, consideration should be given to potential adverse effects on the fetus should spontaneous ovulation and unplanned pregnancy occur. This review highlights the current issues surrounding PCOS and provides a critical appraisal of treatment options.

Adrenarche and polycystic ovary syndrome: a tale of two hypotheses.

Polycystic ovary syndrome (PCOS) is an extremely common endocrine disorder affecting young women, with the potential for both reproductive and non-reproductive adverse outcomes. While oligomenorrhea, hyperandrogenism, and cystic ovarian morphology are recognized characteristics of this syndrome, the origin of these disturbances is not always apparent. During normal growth and development, adrenarche, the prepubertal onset of adrenal androgen secretion, results phenotypically in pubarche. Gonadarche, which is the ovarian response to gonadotropin releasing hormone-mediated gonadotropin secretion, also occurs, leading to reproductive competence, namely the establishment of ovulatory cycles, repeatedly. In this mini-review, an overview of adrenarche and gonadarche are presented, followed by two hypotheses. The first describes an evolutionary role for adrenarche: an advantage in the attainment of reproductive competence. The second proposes that the path to PCOS be viewed from a developmental perspective, namely, that PCOS is a maladaptation of the processes that lead to reproductive competence in women. Its defining characteristics of oligomenorrhea, hyperandrogenism, and cystic ovarian morphology are the final common pathway of multiple possible derangements. Elucidating and understanding these maladaptive processes will be the key to future endeavors at prevention and treatment of this common reproductive disorder.

Thyroid disease and other endocrine disorders in pregnancy.

Endocrine disorders, in particular, thyroid disorders, are common in pregnancy. The endocrine adaptation to pregnancy, need for adequate iodine supplementation, and thyroxine replacement are presented. In addition, autoimmune diseases of the thyroid and pituitary that may occur subsequent to the immune changes of pregnancy and the postpartum period are discussed. A brief account of the presentation of other endocrine disorders (ie, pituitary,parathyroid, calcium, adrenal and gonadal disorders) also is given, along with their evaluation and management.