Novel Formative Approach of the ESAP-ITE Provides Strong Predictive Value for ABIM Certification Outcomes.

Background: The Endocrine Self-Assessment Program In-Training Examination (ESAP-ITE) has the novel formative approach of allowing open access to all questions and answers after secure examination administration is complete, resulting in the creation of an entirely new in-training examination annually.

Objective: To determine whether scores on the novel ESAP-ITE predict pass/fail outcomes on the American Board of Internal Medicine Endocrinology, Diabetes, and Metabolism Certification Examination (ABIM-ECE).

Methods: All endocrine fellows-in-training who took the ESAP-ITE between 2016 and 2019 and then subsequently attempted the ABIM-ECE within the same calendar year were included (n = 982).

Gestational Primary Hyperparathyroidism Due to Ectopic Parathyroid Adenoma: Case Report and Literature Review.

Gestational primary hyperparathyroidism (GPHPT) is a rare condition with fewer than 200 cases reported. We present the case of a 21-year-old woman who presented at 10 weeks' gestation with severe hypercalcemia. Laboratory investigation was consistent with primary hyperparathyroidism.

Medical Management of Osteoporosis for Elective Spine Surgery.

Over 50 million Americans have low bone mass. Poor bone quality is known to complicate spinal fusion surgery, which relies on strong bony purchase to be effective. Unfortunately, many spine surgeons do not perform routine workups for either osteoporosis or osteomalacia.

Electrolyte disorders associated with cancer.

Patients with malignancies commonly experience abnormalities in serum electrolytes, including hyponatremia, hypokalemia, hyperkalemia, hypophosphatemia, and hypercalcemia. In many cases, the causes of these electolyte disturbances are due to common etiologies not unique to the underlying cancer. However, at other times, these electrolyte disorders signal the presence of paraneoplastic processes and portend a poor prognosis.

Osteoporosis treatment and prevention for postmenopausal women: current and future therapeutic options.

Osteoporosis, a "silent disease," is often unrecognized until fracture. Lifestyle modification with nutritional counseling is recommended during menopausal transition. Bone density testing is recommended for women aged 65 years and older, younger postmenopausal women with risk factors, or to follow therapy.

Onco-nephrology: the pathophysiology and treatment of malignancy-associated hypercalcemia.

Hypercalcemia complicates the course of 10%-30% of all patients with malignancies and can be a sign of very poor prognosis and advanced malignancy. Prompt recognition of the nonspecific signs and symptoms of hypercalcemia and institution of therapy can be lifesaving, affording the opportunity to address the underlying etiology. The mechanisms of malignancy-associated hypercalcemia generally fall into three categories: humoral hypercalcemia due to secreted factors (such as parathyroid-related hormone), local osteolysis due to tumor invasion of bone, and absorptive hypercalcemia due to excess vitamin D produced by malignancies.

Treatment of postmenopausal osteoporosis in a patient with celiac disease.

Background: A 62-year-old postmenopausal woman with a family history of breast cancer, mild gastroesophageal reflux disease, iron-deficient anemia and declining BMD was seen in a specialist center for the evaluation and management of osteoporosis.

Investigations: Analysis of tissue transglutaminase IgA, endoscopic biopsy, serial BMD scans, FRAX calculation of osteoporotic fracture risk, Gail model calculation of breast cancer risk, assessment of blood vitamin D concentration and secondary evaluation for osteoporosis.

Diagnosis: Osteoporosis, persistent after 12 years of hormone replacement therapy, and celiac disease.

Phosphaturic mesenchymal tumor diagnosed by fine-needle aspiration and core biopsy: a case report and review of literature.

Oncogenic (tumor-induced) osteomalacia is a rare paraneoplastic syndrome of phosphate wasting that is frequently associated with phosphaturic mesenchymal tumor (PMT). As the cytologic features of this tumor apparently have not been reported, we describe the fine-needle aspiration (FNA) findings for PMT that arose from the gluteal soft tissue in a patient with hypophosphatemia and multiple fractures secondary to osteomalacia. Smears from the computerized tomography (CT)-guided FNA showed groups of spindle cells having elongated nuclei, fine to moderately coarsely granular chromatin, inconspicuous nucleoli, and delicate cytoplasm.

Combination therapy for treatment of osteoporosis: A review.

Combination therapy for osteoporosis has been tested in small trials of short duration with various combinations. Pertinent human and animal randomized clinical trial data were identified through Medline and reviewed with a focus on the risks and benefits of different types of combination therapies. Improvements in bone density were found in some, but not all, combinations.

The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway.

Recent reports suggest that androgens increase FSHbeta transcription directly via the androgen receptor and by modulating activin signaling. Estrogens may also regulate FSHbeta transcription in part through the activin system. Activin signaling can be regulated extracellularly via activin, inhibin, or follistatin (FS) or intracellularly via the Smad proteins.

Stimulation of FSHbeta transcription by blockade of endogenous pituitary follistatin production: Efficacy of adenoviral-delivered antisense RNA in the rat.

This study investigated FSHbeta transcriptional responses to the suppression of endogenous follistatin (FST) production using FST antisense RNA (FST-AS) expressing adenovirus constructs in female rat pituitary cells in vitro. Adenoviral delivery systems were characterized and optimized using an adenovirus-green fluorescent protein construct, and maximal infection (85-90% of cells) was seen 48 h post adenovirus treatment. A 424 bp fragment, which included the translational start site and exons 1-3 of the rat FST gene, was subcloned in the reverse orientation into an adenovirus vector.

Pituitary adenylate cyclase activating polypeptide messenger RNA in the paraventricular nucleus and anterior pituitary during the rat estrous cycle.

The neuropeptide pituitary adenylate cyclase activating polypeptide (ADCYAP 1, or PACAP) has been demonstrated to enhance gonadotropin-releasing hormone (GnRH)-induced gonadotropin secretion and regulate gonadotropin subunit gene expression in cultures of anterior pituitary cells. In the present study, we used in situ hybridization and real-time polymerase chain reaction to examine the expression of Pacap mRNA within the paraventricular nucleus (PVN) and anterior pituitary throughout the estrous cycle of the rat. Levels of luteinizing hormone in serum and pituitary gonadotropin subunit mRNAs were evaluated and displayed cyclic fluctuations similar to those reported previously.

Pituitary follistatin gene expression in female rats: evidence that inhibin regulates transcription.

Follistatin (FS), along with the members of the transforming growth factor beta family activin and inhibin, are important regulators of FSH secretion and messenger RNA production. While activin and inhibin appear to function as tonic modulators of FSH (stimulatory and inhibitory, respectively), dynamic changes in FS are noted through the estrous cycle and under varying physiological experimental paradigms. This suggests that FS is a major contributor to the precisely coordinated secretion of FSH that maintains reproductive function.

Regulation of luteinizing hormone-beta and follicle-stimulating hormone (FSH)-beta gene transcription by androgens: testosterone directly stimulates FSH-beta transcription independent from its role on follistatin gene expression.

The gonadotropin beta-subunit mRNAs are differentially regulated by androgens. Testosterone (T) suppresses LH-beta and increases FSH-beta. We aimed to determine whether androgens regulate LH-beta and FSH-beta transcription [as measured by changes in primary transcript (PT)] and to determine whether androgens act directly on FSH-beta or via the intrapituitary activin/follistatin (FS) system.

Differential expression of the pituitary gonadotropin subunit genes during male rat sexual maturation: reciprocal relationship between hypothalamic pituitary adenylate cyclase-activating polypeptide and follicle-stimulating hormone beta expression.

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to differentially regulate the expression of the gonadotropin subunit genes in cultures of rat pituitary cells. PACAP is expressed within the hypothalamus, and concentrations of PACAP are 2- to 4-fold higher in the portal circulation than in the general circulation. Therefore, PACAP is a candidate regulator of pituitary function.

GnRH pulse frequency modulation of gonadotropin subunit gene transcription in normal gonadotropes-assessment by primary transcript assay provides evidence for roles of GnRH and follistatin.

We examined the time course of action of GnRH pulse frequency on gonadotropin subunit gene transcription and assessed the roles of GnRH, follistatin (FS), and activin on differential transcription of the LHbeta and FSHbeta genes. GnRH-deficient male rats were pulsed with 25 ng GnRH either every 30 min (fast frequency) or every 240 min (slow frequency) for 1-24 h. Both GnRH frequencies increased alpha primary transcript (PT) 5-fold within 6 h, but only fast frequency GnRH increased alpha mRNA.

Evidence that PACAP and GnRH down-regulate follicle-stimulating hormone-beta mRNA levels by stimulating follistatin gene expression: effects on folliculostellate cells, gonadotrophs and LbetaT2 gonadotroph cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates alpha-subunit transcription and lengthens LH-beta mRNA transcripts, but reduces FSH-beta mRNA levels in rat pituitary cell cultures. PACAP also stimulates follistatin transcription, an effect which may explain the decrease in FSH-beta mRNA. To begin to investigate the cells in which PACAP activates the follistatin gene, quantitative in situ hybridization for follistatin mRNA combined with immunostaining for LHbeta and S100 protein was performed.