Raymond C. Mellinger

COLON CANCER AND POLYPS IN ACROMEGALY: INCREASED RISK ASSOCIATED WITH FAMILY HISTORY OF COLON CANCER

A cohort of 52 subjects diagnosed with acromegaly in southeastern Michigan and northern Ohio between 1935 and 1985 were followed to determine the incidence of colon cancer and polyps. Medical records were reviewed, subjects or their next‐of‐kin were interviewed, and screening examinations of the colon were offered to the living patients who were located. Data on demographics, personal histories of cancer and colon polyps, family history of colon cancer, and cure from acromegaly were obtained for both living and deceased subjects. The risk for colon cancer compared to the general population was estimated using standardized incidence ratios (SIRs). The expected number of cases was determined utilizing age, sex and race‐specific rates provided by the cancer registry in southeastern Michigan. Among the 52 subjects, one could not be located and nine were deceased, none from colon cancer, with one known to have a history of colon polyps. Of 13 (31 %) who declined the screening physical, one had a history of polyps and none reported a history of colon cancer. Two of 29 screened patients were found to have right‐sided adenocarcinoma of the colon. Of the entire cohort, eight people (including one deceased) had a current or previous diagnosis of polyps, with five known to be histologically adenomatous. The SIR for colon cancer was 4.7 (95% confidence interval 0.6–17.1). Seven subjects, including the two with detected adenocarcinoma and four of the six living subjects with polyps only, reported a family history of colon cancer. The SIR for the subset of subjects with a family history of colon cancer was 29.1 (95% confidence interval of 3.5–104.6). Logistic regression analysis of the subset of the acromegalic cohort that was screened demonstrated that family history of colon cancer and male gender were predictive of the presence of colonic neoplasms at P< 0.001 and P< 0.009, respectively. This study supports the association between acromegaly and colon cancer reported by others and suggests that an increased risk of colon cancer in these patients may be associated with a family history of colon cancer. We recommend that patients with acromegaly routinely undergo colon cancer screening, particularly those with a positive family history for colon malignancies.

The Effect of Clomiphene Citrate in Male Infertility

18 infertile men were studied in order to determine the effect of clomiphene citrate on oligospermia. Total gonadotropins were determined as were follicular stimulating and luteinizing hormone levels. Urinary 17-ketosteroids were assayed and fractionization done by gas-liquid chromatography. Testosterone glucuonide was likewise determined by gas-liquid chromatography. Multiple semen analyses were performed on specimens collected in the clinic after a period of abstinence of 3 days. Administration of clomiphene to oligospermic male subjects resulted in marked testicular stimulation. Augmented urinary gonadotropins were observed in 10 of 11 subjects. 2 patients with congenital absence of gonadotropins failed to respond to the drug. A case of delayed puberty had a moderate response. Augmented sperm counts irregularly sustained and unaccompanied by increased motility were observed in 10 of 13 subjects. 3 subjects had a marked decrease in sperm counts which subsequently returned to normal. 2 subjects with maturation arrest of spermatogenesis failed to respond with sperm maturation. Increased urinary 17-ketosteroids were observed in 6 of 7 subjects with normal gonadotropins. In 3 of 4 subjects 1 of whom had maturation arrest of spermatogenesis and elevated gonadtropins a marked increase in urinary testosterone glucuronide occurred. Side effects were minimal. However fertility remained absent in all cases.

On the incidence of senile osteoporosis.

Excerpt Physicians generally agree that senile osteoporosis is encountered with increasing frequency, presumably due to the lengthening life span achieved during the last several decades. Back pain...

The effects of clomiphene citrate in patients with pituitary-gonadal disorders

Abstract The following observations in 41 women and 15 men receiving clomiphene citrate illustrate its effects and imply a primary mechanism of action. Antiestrogenic effects. Vaginal cornification, cervical mucus arborization, and endometrial growth were inhibited. These effects were related to the dose and duration of therapy. Hot flushes occurred in 13 of 33 women with functioning ovaries. Amelioration of fibrocystic mastitis resulted in each of 5 patients treated. Estrogenic effects. In estrogen-deficient women, hot flushes and gonadotropin titers were decreased. Gonadotropin stimulating effects. In an estrogen-treated patient with Turners syndrome, the suppressed gonadotropin secretion was increased.In all male patients with normal urinary gonadotropins,FSH andLH increased proportionately, in females, total gonadotropin excretion increased in 4 and decreased in 1 patient.The titer was increased in 1 of 2 patients with reduced excretion of gonadotropins, and decreased in the other. In 3 patients without urinary gonadotropins, no change was observed. Gonadal stimulating effects. A moderate to marked increase in sperm counts was observed in 10 out of 11 oligospermic males.In 25 anovulatory women, ovulation was induced in 35 of 77 cycles. Regular ovulation was induced in 7 patients in whom it was previously irregular.Urinary neutral 17-ketosteroids increased in 5 males with normal titers of gonadotropins. No definite increase was found in 3 gonadotropin-deficient males or in any of the female patients.These data are interpreted to indicate that clomiphene citrate, a weak estrogen, inhibits the effects of endogenous estrogen at the cellular level, which produces a reflex hypersecretion of gonadotropin and consequent gonadal stimulation.

Pituitary function in the deprivation syndrome

Fasting serum growth hormone values of infants and some children with thedeprivation syndrome were increased, providing tests were done before unrestricted feeding. Pituitary growth hormone and adrenocorticotropic hormone release were unresponsive to hypoglycemia only in children (5/7); however, some (3/5) had normal or increased serum growth hormone values on admission, and all had normal metyrapone tests. One severely emaciated child probably had deficient growth hormone and thyroid function. Control infants with growth failure due to undernutrition with an organic basis had elevated fasting serum growth hormone values. Insensitivity to hypoglycemia was not related to the severity of the linear growth failure and probably does not reflect growth hormone deficiency at the target organ.

EVALUATION OF THYROID FUNCTION DURING GROWTH HORMONE THERAPY

Decrease in the blood levels of PBI, in the thyroidal uptake of iodine, and diminished effect of TRH on TSH release have been reported to occur during growth hormone administration. We assessed thyroid function indices in two groups of growth hormone deficient children before and during long-term HGH therapy. Eight patients were given TSH prior and at 2, 4, and 6 mo of growth hormone treatment. In four other children, the disposal rates of simultaneously administered I125-T4 and I131-T3 were measured before and at 2 and 6 mo after initiation of HGH replacement. Blood levels of TSH, T3, T4, TBG capacity, and the T3 resin uptake were obtained at the time of each study. Growth hormone therapy did not affect the blood levels of T4, T3, TSH, TBG capacity, the T3 resin uptake, the thyroidal response to exogenous TSH, nor the disposal rates of thyroid hormones.

Effect of growth hormone on urinary 17-ketosteroids in childhood.

Abstract Studies of the urinary 17-ketosteroids of eight growth hormone-deficient prepubertal children disclosed levels much lower than those of normal subjects of similar age. After 2 yr of growth hormone administration, both C 19 O 2 and C 19 O 3 androgen metabolites increased substantially in all subjects, but urinary corticoid levels had not increased proportionately. Androsterone levels demonstrated the most significant increase. 17-KS excretion in response to ACTH was increased after growth hormone therapy, although the corticoid response was not proportionately augmented. Growth hormone is proposed as one factor responsible for the increasing androgen secretion that characterizes the maturing childhood adrenal.

Nitrogen metabolism in growth hormone-deficient children receiving oxandrolone and human growth hormone

Five prepubertal growth hormone-deficient children were treated with oxandrolone (0.1 mg/kg/day) and human growth hormone (HGH) 2 mg three times weekly alone and in combination. Average nitrogen retained (mg/kg/day) was calculated from 9-day balance data obtained at the beginning and end of each 6-mo treatment period. Oxandrolone increased the range of nitrogen retention from control values of 2.5–50 to 20.4–107.1, which was statistically significant. Persistently increased nitrogen retention was demonstrable at the end of 6 mo of oxandrolone therapy. Addition of HGH further enhanced the anabolic effect (67.7–139.3), which also was statistically significant and persistent to the end of 6 mo of combination therapy (57.4–114.3). Despite continued HGH treatment with-drawal of oxandrolone was associated with a drop to pretreatment values by the end of 6 mo (0.8–38.4). Oxandrolone and HGH have synergistic anabolic effects which probably involve different mechanisms. During some balance periods, nitrogen retention was calculated by determination of 15N excretion after oral administration of labeled glycine. Results were similar but lacked statistical significance. The smallest increment in height for 1-yr advancement in bone age while receiving oxandrolone was 2.17 inches.

The Effects of Clomiphene Citrate in Patients with Pituitary-gonadal Disorders.

Excerpt Clomiphene citrate (MRL-41), a derivative of the synthetic estrogen TACE, is a new drug with unique properties of therapeutic potential for such diversified conditions as amenorrhea, anovul...