Harold E. Carlson

Osteoporosis and fracture risk in people with schizophrenia.

Purpose of review Excessive bone mineral density (BMD) loss has been associated with schizophrenia, but its mechanisms and clinical implications are less clear. The aim of this review was to summarize the risk of osteoporosis and bone fractures in schizophrenia patients. Moreover, we aimed to examine the impact of antipsychotic-induced hyperprolactinemia on bone metabolism. Recent findings Fifteen of 16 studies (93.8%) reported lower BMD or higher prevalence of osteoporosis in at least one region, or in at least one subgroup of schizophrenia patients compared with controls, but results were inconsistent across measured areas. Higher fracture risk was associated with schizophrenia in 2/2 studies (independently: n = 1), and 3/4 studies with antipsychotics. Reasons for this difference include insufficient exercise, poor nutrition, smoking, alcohol use, and low vitamin D levels. Altogether, 9/15 (60.0%) studies examining the relationship between antipsychotic-induced hyperprolactinemia and BMD loss found some effects of hyperprolactinemia. However, results were mixed, samples and effects were small, and only two studies were prospective. Summary Schizophrenia is associated with reduced BMD and fracture risk. Prevention, early detection, and intervention are required. The relative contributions of antipsychotic-related hyperprolactinemia and unhealthy lifestyle behaviors remain unclear, needing to be assessed in well designed, prospective studies, including bone turnover markers as intermediary endpoints.

Absorption of Levothyroxine When Coadministered with Various Calcium Formulations

BACKGROUND Calcium carbonate is a commonly used dietary supplement and has been shown to interfere with levothyroxine absorption. However, calcium citrate, which is also used for supplementation purposes, has not been studied previously and calcium acetate, which is used to treat hyperphosphatemia in renal failure, has been reported to show little or no interference with levothyroxine absorption in a retrospective pharmacoepidemiologic study. We aimed to compare the effect of these three calcium formulations on levothyroxine absorption. MATERIALS AND METHODS The study was conducted in eight healthy, euthyroid adults. We performed single-dose pharmacokinetic studies in which we measured levothyroxine absorption when given alone or when coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. Serum thyroxine was measured at intervals over a 6-hour period after ingestion of the study drugs. RESULTS Coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone. CONCLUSIONS Contrary to a prior report, our data suggest that calcium acetate interferes with levothyroxine absorption in a manner similar to that seen with calcium carbonate and calcium citrate. Although the effect of calcium is modest compared with some other medications previously studied, hypothyroid patients should be cautioned to take their levothyroxine well-separated from all of these calcium formulations.

Gynaecomastia—Pathophysiology, Diagnosis and Treatment

Gynaecomastia (enlargement of the male breast tissue) is a common finding in the general population. Most cases of gynaecomastia are benign and of cosmetic, rather than clinical, importance. However, the condition might cause local pain and tenderness, could occasionally be the result of a serious underlying illness or a medication, or be inherited. Breast cancer in men is much less common than benign gynaecomastia, and the two conditions can usually be distinguished by a careful physical examination. Estrogens are known to stimulate the growth of breast tissue, whereas androgens inhibit it; most cases of gynaecomastia result from deficient androgen action or excessive estrogen action in the breast tissue. In some cases, such as pubertal gynaecomastia, the breast enlargement resolves spontaneously. In other situations, more active treatment might be required to correct an underlying condition (such as hyperthyroidism or a benign Leydig cell tumour of the testis) or medications that could cause breast enlargement (such as spironolactone) might need to be discontinued. For men with hypogonadism, administration of androgens might be helpful, as might antiestrogen therapy in men with endogenous overproduction of estrogens. Surgery to remove the enlarged breast tissue might be necessary when gynaecomastia does not resolve spontaneously or with medical therapy.

Approach to the Patient with Gynecomastia

Gynecomastia is a common and sometimes distressing condition that may occur in males of all ages. Although most cases have benign causes and many are self-limited, male breast enlargement may also be a sign of underlying systemic disease or drug toxicity. Although rare, male breast cancer must also be considered in the differential diagnosis. A careful diagnostic evaluation should be pursued, tailored to the individual patients circumstances. Treatment may include reassurance, medication, or surgery.

Human adrenal cortex hyperfunction due to LH/hCG.

Adrenal cortex hyperfunction may occasionally be due to stimulation of steroid hormone production by LH/hCG. The recent demonstration of the LH/hCG receptor in a variety of normal and abnormal human adrenal tissues has provided a novel explanation for these clinical observations and offers the possibility of spontaneous remission (as in pregnancy-related hyperfunction) or effective treatment with GnRH-agonists (to down-regulate LH secretion in menopausal patients). Involvement of adrenal LH/hCG receptors should be considered in pregnant or post-menopausal patients with ACTH-independent Cushings syndrome or androgen excess. Additional investigations are needed to better define the role of the LH/hCG receptor in the normal adult and fetal human adrenal and to understand how this system is excessively activated in rare cases of human disease.

Differential Tissue Regulation of the Insulin-Like Growth Factors in Rats Bearing the MStT/W15 Pituitary Tumor

The content of insulin-like growth factors, IGF-I and IGF-II, was measured in tissues of rats bearing a transplantable mammosomatotrophic tumor, MStT/W15. Serum IGF-I was elevated in tumor-implanted rats [2,557 +/- (SE) 419 vs. 891 +/- 100 ng/ml], and tumor tissue concentrations of IGF-I were increased (321 +/- 16 ng/g) in comparison to control liver tissue (160 +/- 5 ng/g) or control pituitary (80 +/- 3 ng/g). The IGF-I levels were significantly increased in most peripheral tissues in the tumor-bearing rats with the exception of the liver. In support of this finding, messenger RNA for prepro IGF-I was likewise not increased in the livers of tumor-bearing rats, nor was there an increase in the growth hormone-dependent IGF-binding protein, BP-3, in the liver or serum of these animals. All tumors had detectable levels of prepro IGF-I mRNA which was, however, less than 50% of that noted in normal control liver. The tumors also expressed an IGF-BP which was identified as IGF-BP-2 by immunoblotting. Serum concentrations of IGF-II were similar in control and tumor-bearing animals (approximately 70 ng/ml). IGF-II levels in the tumor (90 +/- 5 ng/g) were significantly higher than levels in control liver (34 +/- 2 ng/g), but similar to those found in normal pituitary (165 +/- 24 ng/g). In peripheral tissues, IGF-II concentrations were selectively increased in skeletal muscle and heart of tumor-bearing rats. These data demonstrate tissue-specific regulation of IGF-I and IGF-II. Paradoxically, the liver does not appear to be stimulated over control levels by high serum growth hormone levels, since neither IGF-I peptide, IGF-I mRNA, nor IGF-BP-3 levels are increased in livers of tumor-bearing rats. This suggests that the increase in serum IGF-I in these animals is due to increased production of IGF-I by the tumors themselves and by nonhepatic peripheral tissues and further that hepatic responsiveness to growth hormone is diminished in these tumor-bearing animals.

Lack of association between hyperprolactinemia and colon carcinoma.

Abstract Two recent studies reported that many patients with colorectal carcinoma have elevated serum prolactin (PRL) concentrations and have suggested ectopic PRL secretion as the cause. In the present study, serum PRL was minimally elevated in 16 of 116 colon cancer patients and 2 of 25 control subjects; medications or chemotherapy appeared to be responsible for the PRL elevations in 11 of 16 cancer patients. Serum PRL was not correlated with either plasma carcinoembryonic antigen or disease stage. Preoperative and postoperative serum PRL concentrations were similar in 26 evaluated patients. None of 19 colorectal tumors was positive for PRL staining by immunohistochemistry. Thus, we could not confirm previous reports of frequent hyperprolactinemia in patients with colorectal cancer; factors such as medications, anxiety, pain, and nausea may have raised serum PRL in these earlier studies. Serum PRL is not a useful marker for colon carcinoma, at least in patients in the United States.

Postmenopausal uterine bleeding due to estrogen production by gonadotropin-secreting lung tumors

Two postmenopausal women are described who had uterine bleeding due to hormone production by lung tumors--a large cell carcinoma in one case and a choriocarcinoma in the other. Both tumors stained positively for one or more placental peptides (human chorionic gonadotropin [hCG], placental lactogen, or pregnancy-specific beta-1 glycoprotein) and both patients had extremely elevated serum levels of hCG, suggesting the tumors had some placental-like endocrine function. Clinical and hormonal data supported the concept that the uterine bleeding resulted from estrogen excess due to steroid bio-transformation by the tumors.

Rupture of a craniopharyngioma cyst following trauma: a case report

There have been only 20 reported cases of non-surgical rupture of a craniopharyngioma cyst, with only 3 cases secondary to trauma. Here we present a rare case of temporary shrinkage of a cystic craniopharyngioma following head trauma. After a motor vehicle accident in May 2001, a 61-year old woman began to have blurred vision and headaches. Magnetic resonance imaging (MRI) of the head revealed a primarily cystic mass measuring approximately two centimeters, involving the sellar and suprasellar area with compression of the pituitary. Visual field testing showed a left hemianopsia and the patient was referred for surgical evaluation. Transsphenoidal drainage of the cystic lesion in November 2001 provided histologic confirmation of the craniopharyngioma. Post-operative MRI showed cyst reduction and visual fields improved. Late in 2002, the patient again experienced progressive visual loss. Repeat MRI revealed a recurrent cystic craniopharyngioma, now measuring approximately three centimeters with subfrontal and parasellar extension and compression of the optic chiasm. A bifrontal surgical approach was advocated; however, prior to the scheduled surgery, the patient sustained a fall with trauma to the head. Following this event she experienced dramatic improvement in her headache and vision and repeat MRI showed the cystic lesion to be significantly decreased in size. Spontaneous rupture of craniopharyngioma cysts is uncommon but has been reported with increasing frequency. It is, however, exceedingly rare for a cyst to rupture following trauma.

Drugs and Pituitary Function

Publisher Summary Many drugs, both therapeutic and recreational, alter the function of the pituitary gland, usually as a side effect unrelated to the primary indication for which the drug was given. Consumption of beverages containing ethanol may alter pituitary function in several ways: by direct effects on the brain or pituitary gland; by altering the function of end organs (e.g., testis) and provoking feedback-mediated changes in pituitary hormone secretion; and by modifying the peripheral metabolism or action of hormones with resulting effects on pituitary function. In some studies, the acute administration of ethanol has been reported to stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion. Cigarette smoking results in the acute release of several pituitary hormones, and the effects appear to be due to nicotine. Several studies have reported increases in plasma cortisol, DHEA, ACTH and bendorphin/ β-lipotropin in response to smoking one or more medium- or high-nicotine cigarettes; sham smoking or smoking low-nicotine cigarettes had no such effect. Acute administration of opiates (e.g., morphine, heroin, codeine, fentanyl, β-endorphin, enkephalins) has profound and generally consistent effects on human pituitary function. In males, serum LH is lowered, followed by a fall in serum testosterone. In females, opiates suppress serum LH in premenopausal subjects, often resulting in irregular menses or amenorrhea. Effects of various other substances and hormones are discussed in this chapter.