Wolfram E. Nolten

Microdeletions in the Y Chromosome of Infertile Men

Background Some infertile men with azoospermia or severe oligospermia have small deletions in regions of the Y chromosome. However, the frequency of such microdeletions among men with infertility in general is unknown. We sought to determine the prevalence of Y-chromosome microdeletions among infertile men and to correlate the clinical presentation of the men with specific deletions. Methods We studied 200 consecutive infertile men. Each man was evaluated comprehensively for known causes of infertility, and Y-chromosome microdeletions were studied with use of the polymerase chain reaction to amplify specific regions of the chromosome. The Y chromosomes of 200 normal men were also analyzed. Results Fourteen infertile men (7 percent) and four normal men (2 percent) had microdeletions of the Y chromosome. Nine of the infertile men had azoospermia or severe oligospermia (sperm concentration, <5 million per milliliter), four had oligospermia (sperm concentration, 5 million to <20 million per milliliter), and one had normospermia (sperm concentration, ≥20 million per milliliter). The size and location of the deletions varied and did not correlate with the severity of spermatogenic failure. The fathers of six infertile men with microdeletions were studied; two had the same deletions as their sons, and four had no deletions. Conclusions A small proportion of men with infertility have Y-chromosome microdeletions, but the size and position of the deletions correlate poorly with the severity of spermatogenic failure, and a deletion does not preclude the presence of viable sperm and possible conception.

Review: Subclinical Hypothyroidism in the Elderly: To Treat or Not To Treat?

Patients with subclinical hypothyroidism (SCH) have normal concentrations of thyroid hormone and elevated thyrotropin (TSH) levels. These individuals may experience mild symptoms of hypothyroidism. Such symptoms are nonspecific and also can be associated with aging or nonthyroidal illness. SCH is not uncommon in the elderly, particularly in females with positive thyroid antibodies and in those who have undergone partial thyroidectomy or I131 treatment for Graves’ disease. Patients with SCH with markedly increased TSH levels or high-titer thyroid antibodies are at higher risk of progressing to overt hypothyroidism. Management options include observation only, with long-term follow up, or substitution with thyroid hormone. Replacement will prevent the development of overt hypothyroidism when reliable follow-up cannot be assured and may improve subtle, nonspecific symptoms of thyroid hormone deficiency. If a decision in favor of replacement therapy has been made, the dose of thyroid hormone should be increased gradually with the objective of returning the TSH level to normal without inappropriately elevating the serum thyroxine concentration. The patient should be carefully observed to see if hypothyroid symptoms, mental status or cardiac function improve with therapy. Continued administration of thyroid hormone would serve prophylactic purposes even if improvement did not occur.

Hazards of treating osteoporosis and hypertension concurrently with calcium, vitamin D, and distal diuretics.

An adverse drug interaction may result from as many as 8 percent of all prescriptions written.’ The elderly population, in which there is an increase in all types of illnesses, may be at greater risk for adverse drug interactions than the population as a whole, as common conditions of aging are more frequently recognized and treated. In postmenopausal women, the treatment for two commonly occurring conditions-osteoporosis and hypertension-can have a synergistic effect resulting in severe hypercalcemia. Earlier investigators have described the association between thiazide diuretics and hypercalcemia. 2-6 Calcium andl or vitamin D supplementation can potentiate and exacerbate the hypercalcemic effects of distal diuretics. The presented case illustrates the difficulties and dangers of concurrently treating hypertension and osteoporosis in the elderly.

Testosterone free index correlates best with dehydroepiandrosterone sulfate

Correlation coefficients for dehydroepiandrosterone sulfate (DHEAS) were determined in women on menotropin. DHEAS was significantly correlated with testosterone free index (TFI), 0.78**; percentage free testosterone (%FT), 0.66**; androstenedione (delta 4A), 0.66*; luteinizing hormone (LH), 0.55**; LH/follicle-stimulating hormone (FSH) ratio, 0.55**; 17-OH-progesterone (17-P), 0.55**; testosterone (T), 0.53**; weight (WT), 0.40**, urinary estriol glucuronide (E3G), 0.33*; and free cortisol index (FFI), 0.32*, with 43 df but not with prolactin (PRL), 0.25. Normal male DHEAS (3.5 +/- 1.2, 25) (microgram/ml; mean +/- standard deviation, n) was higher than normal female DHEAS (2.4 +/- 1.1, 27), P less than 0.01 and DHEAS in women on oral contraceptives (1.9 +/- 1.1, 17) was slightly lower than in normal females, P greater than 0.2. In the combined population (male, female, and females on oral contraceptives) DHEAS was correlated with TFI (0.56**), T (0.54**), %FT (0.52**), delta 4A (0.40**), and age (-0.40**) with 66 df and 17-P (0.30*) with 54 df. TFI appears to be one determinant of plasma DHEAS, **P less than 0.01. *P less than 0.05.

Effects of iodinated glycerol on thyroid function studies in elderly nursing home residents.

Iodinated glycerol is used as a mucolytic expectorant in the treatment of respiratory disorders. Iodine can inhibit the biosynthesis of thyroid hormone and induce hypothyroidism, particularly in patients with a history of thyroid disease. Such effects have not been reported in individuals without known thyroid disease who are being treated with organically bound iodine in the form of iodinated glycerol. In the course of a thyroid screening program for nursing home residents, eight subjects were identified who were being treated with iodinated glycerol.

Follow-up of mild hypothyroidism in a nursing home

The course of untreated mild hypothyroidism was followed in 67 nursing home residents (mean age 78 years). The diagnosis was based on a normal free thyroxine index (FTI) and elevated thyrotropin concentration (TSH 4.6 to 15.0 μIU/mL, nl ≤ 4.5 μIU/mL). FTI and TSH were measured in follow‐up> 42–378 (mean 161) days after the diagnosis of mild hypothyroidism had been made. In 45 patients initial TSH was <6.8 μIU/mL; in 23 of these subjects TSH returned to normal during the observation period, whereas in 22 TSH remained elevated. In all 22 residents whose initial TSH was >6.8 μIU/mL, TSH remained elevated at follow‐up. In 4 subjects whose initial TSH concentrations ranged from 5.0 to 9.6 μIU/ml, FTI fell below normal 91–141 days after the diagnosis of mild hypothyroidism was made. Clinical progression of the signs or symptoms of hypothyroidism was not detected in the 4 patients who developed hypothyroxinemia. Three demonstrated positive thyroid antibody titers, and 1 had myasthenia gravis. These observations suggest a need for replacement therapy in debilitated patients with mild hypothyroidism and evidence of thyroid autoimmunity.

Thyroid Stimulating Hormone Elevation without Antithyroid Antibody Elevation in Nursing Home Patients

Objectives: To investigate the relationship between antithyroid antibody elevation and thyrotropin (TSH) elevation.