Patrizia Del Monte

The impact of obesity on hormonal parameters in hirsute and nonhirsute women.

The influence of obesity on sex hormone-binding globulin (SHBG) and androgen concentrations in hirsute and nonhirsute women has been evaluated. The study was performed in 226 hirsute women (88 obese and 138 non-obese) classified as being affected by polycystic ovarian syndrome (PCOS) or by idiopathic hirsutism (IH) and in 100 nonhirsute control women ([C] 60 lean and 40 obese). SHBG, free testosterone (fT), androstenedione (A), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and gonadotropin levels were measured during the first week of the menstrual cycle by radioimmunoassay (RIA). A significant negative correlation between SHBG and body mass index (BMI) was observed in PCOS, IH, and C women. In obese women--whether PCOS, IH, or C-fT levels were significantly higher and, conversely, SHBG levels were lower than in non-obese women. A negative correlation between SHBG and fT was evidenced in each group. Upper-body obesity was associated with lower SHBG and higher fT levels than lower-body obesity. In conclusion, obesity, particularly upper-body obesity, is associated with a reduction in SHBG and an increase in fT in both nonhirsute and hirsute women.

Endocrine Evaluation in Patients Treated with Interferon-Alpha for Chronic Hepatitis C

The aim of our study was to evaluate the hormonal profile in a group of 31 subjects who underwent recombinant interferon-alpha therapy for chronic active hepatitis C. Hormonal determinations were performed before treatment began and at the end of the 3rd and 6th months of therapy. Free-T4 concentrations, though remaining in the normal range, showed a significant reduction (p < 0.05) after 3 and 6 months of therapy compared with pretreatment levels. A lesser decrease in free-T3 levels was also seen. TSH basal values did not show any variation, while an increased secretory response to TRH stimulation was observed at the end of the 6th month. Thyroglobulin and calcitonin levels remained normal, while an increase in antithyroglobulin and antithyreoperoxidase antibody levels was observed in 4 patients (12.9%). No modifications in the other pituitary hormones or in adrenal and sex steroid concentrations were noticed. A significant increase in IGF-I concentrations (p < 0.05) was observed during treatment, and an inverse correlation was seen between IGF-I and alanine aminotransferase levels (p < 0.01). This study supports the view that interferon treatment can influence thyroid function. The increase in IGF-I concentration observed during therapy may reflect an improvement in patients with hepatic disease, but a direct stimulatory effect of interferon on IGF-I secretion cannot be excluded.

Intrathyroidal parathyroid carcinoma as cause of hypercalcemia and pitfall of localization techniques: clinical and biologic features.

OBJECTIVE To describe an unusual case of intrathyroidal parathyroid carcinoma (PC), which was retrospectively diagnosed in a woman who underwent surgical treatment of a recurrent nodular goiter. METHODS We report the clinical and biologic features of an intrathyroidal PC, discuss the challenges with distinguishing PC from parathyroid adenoma, and review the related literature. RESULTS A 67-year-old woman sought medical attention for dysphagia attributable to the recurrence of a normal functioning multinodular goiter. Thyroid ultrasonography disclosed a 3-cm solid inferior nodule. Because she refused surgical treatment and a trial of levothyroxine was unsuccessful, periodic follow-up examinations were scheduled. At 1-year follow-up, hypercalcemia (12.1 to 12.6 mg/dL) and low phosphorus levels (2.0 to 2.3 mg/dL) were found, and parathyroid hormone (PTH) levels were profoundly increased (481 to 721 pg/mL). Neck ultrasonography showed a large hypoechogenic solid nodule, not clearly cleaved from the right thyroid lobe, which was possibly compatible with an enlarged parathyroid gland; however, a sestamibi scan was negative. During total thyroidectomy, intraoperative frozen sections of the intrathyroid nodule were compatible with nodular goiter with cellular pleomorphism. Final histologic examination showed cellular nests with nuclear pleomorphism and invasive behavior into the thyroid tissue and likely into the vessels, in conjunction with immunohistochemical negativity for thyroglobulin and strong positivity for PTH. These findings were highly suggestive of and supported the diagnosis of PC. Postoperatively, calcium levels normalized, and PTH values declined considerably but remained slightly increased. Vitamin D supplementation helped normalize the PTH levels. The patient has undergone follow-up for 5 years and has shown no morphologic or biochemical signs of tumor recurrence. CONCLUSION PC is a rare entity but should be suspected in patients with hypercalcemia, substantially increased PTH levels, and a neck mass. In such patients, techniques such as sestamibi scanning may fail to localize the neoplasm. Surgical treatment remains the preferred technique for an optimal outcome of the disease. Nevertheless, lifelong follow-up is necessary.

Hypopituitarism in the elderly: two case-reports with heterogeneous presentation

Hypopituitarism (HYPO) is an under-investigated disease in older patients. Symptoms, which may be life-threatening, are aspecific and often attributed to aging and/or related morbidities. We describe here the cases of two elderly patients who were ultimately diagnosed as having HYPO, the clinical presentations and etiologies of which were different. In the first patient, an invasive non-secreting pituitary macroadenoma causing HYPO was detected on brain morphological evaluation for head trauma secondary to falling. Glucocorticoid replacement therapy was started. Thyroid function evaluation showed hyperthyroidism (due to a known toxic multinodular goiter), which was already on treatment with methimazole; ultimately, after withdrawal of the antithyroid drug, secondary hypothyroidism occurred. The patient underwent non-radical pituitary surgery. Cognitive function, gait impairment and falling, which had previously been attributed only to aging, improved markedly after cortisone acetate and L-thyroxine replacement therapy. The second patient was hospitalized one month after the onset of hypotension, edema and pain in the legs, and progressive psychomotor impairment, which ultimately resulted in an intermittent soporous state. She was diagnosed as having global anterior HYPO secondary to empty sella, which caused severe multifaceted clinical and biochemical abnormalities (hyponatremia, pancytopenia, rhabdomyolysis). After treatment with i.v. fluids and hydrocortisone, the patient’s clinical condition and biochemical alterations improved, and normalized over time with oral cortisone acetate and L-thyroxine combination therapy. Several protean symptoms that impair the quality of life of elderly patients are usually ascribed to aging. Such symptoms should be investigated with regard to possible HYPO, treatment of which can result in significant clinical benefit.

Late-Onset Metastasis of Renal Cell Carcinoma into a Hot Thyroid Nodule: An Uncommon Finding Not to Be Overlooked

We report the case of a 74-year-old man with a four-year history of right nephrectomy for clear cell renal carcinoma (CCRC) who was diagnosed with hyperthyroidism. On ultrasound (US), a 5 cm solid isohypoechoic nodule with intranodular vascularization was found in the left thyroid lobe. The nodule was deemed autonomous on 99mTc thyroid scan. Methimazole was started and serum thyroid hormone levels quickly normalized; euthyroidism was maintained with a very low dosage of antithyroid drug. Over time, compressive symptoms and local pain occurred and US revealed growth of the nodule. Total thyroidectomy was performed and the combined histological and immunohistochemical evaluation deemed the nodule compatible with metastasis of CCRC; on 2-year follow-up, no tumor relapse was ascertained. In patients with a history of cancer, a thyroid nodule, even if hyperfunctioning, must be suspected of being a metastasis and investigated. Hot nodules, which are largely benign, may be vulnerable to metastatic colonization owing to their rich vascularization. In these cases, surgery may be curative.

Hyperthyroidism unmasked several years after the medical and radiosurgical treatment of an invasive macroprolactinoma inducing hypopituitarism: a case report

IntroductionMeasuring thyroid stimulating hormone levels alone may be insufficient to appropriately evaluate thyroid function. Reduced thyroid stimulating hormone levels associated to normal/reduced FT4 levels should prompt investigation of pituitary function, on suspicion of hypopituitarism. Pituitary macroadenomas are the most common cause of hypopituitarism; among these, macroprolactinomas are usually treated with dopamine-agonist therapy. Hypopituitarism does not preclude the development of primary hyperthyroidism. This report describes the case of a patient with a final diagnosis of macroprolactinoma inducing hypopituitarism, who subsequently developed hyperthyroidism due to a toxic thyroid nodule.Case presentationA 62-year-old man underwent biochemistry and thyroid function assessment for asthenia. Reduced thyroid stimulating hormone levels were associated to slightly decreased FT4 levels and low-normal FT3 levels; thyroid ultrasonography showed a multinodular goiter. Thyroid scan with 99mTc-pertechnetate revealed an autonomous left nodule with suppression of the surrounding parenchyma. Pituitary investigation showed partial hypopituitarism associated to increased prolactin levels: 182-200 ng/ml. Magnetic resonance imaging revealed a large (2.2 cm) invasive macroadenoma. To avoid a possible high-dose hook effect, the patients serum was diluted; the resulting PRL levels of around 1800 ng/ml prompted the final diagnosis of macroprolactinoma. Reduced libido and erectile dysfunction were ascertained. In addition to replacement therapy with L-thyroxine and testosterone, cabergoline was started and was progressively increased to high doses (4 g/week); this yielded a significant but incomplete reduction of PRL levels (63-99 ng/ml). Sexual function improved. The macroadenoma shrank over the first two years of therapy, but subsequently enlarged slightly. Following stereotactic radiosurgery, the tumor stabilized and prolactin almost normalized (22 ng/ml) on therapy. Over the years, thyroid nodule volume was unmodified, but hyperthyroidism on L-thyroxine therapy was found, and increased FT3 levels with suppressed thyroid stimulating hormone levels were confirmed off-therapy. Thyroid scan confirmed the left autonomous nodule, which was successfully treated with methimazole.ConclusionReduced thyroid stimulating hormone levels associated to normal/reduced free-thyroid hormone levels may be the first clue to unsuspected hypopituitarism. Moderately increased prolactin levels in the presence of a large macroadenoma warrant serum dilution in order to avoid a possible hook effect. Stereotactic radiosurgery is a useful non-invasive tool in the management of pituitary tumors. A pre-toxic thyroid nodule with low secretory activity may initially be masked by the coexistence of secondary hypothyroidism, but may lead to overt hyperthyroidism over time.

Osteoporosis in an elderly man as interplay of multiple diseases.

Osteoporosis continues to be overlooked in men. In this population, osteoporosis is often related to corticosteroid use, alcohol abuse and hypogonadism. Osteoporosis-related fractures often result in long-term hospitalization with a consequent decline in quality of life. Bone mass density (BMD) in the aging male population is positively associated with endogenous androgen and estrogen levels, and testosterone treatment improves bone mineralization in hypogonadal men. Type 1 hereditary hemochromatosis (HH), is an autosomal recessive disorder associated with a mutation of the HFE (high iron Fe, hemochromatosis) gene, leading to a progressive iron overload which impairs the function of many organs. HH is an unusual cause of hypogonadotropic hypogonadism. In addition, hemochromatosis per se causes significant bone loss that cannot be solely explained by hypogonadism. A 71-year-old man was referred to our endocrinology unit from the Center of Metabolic Bone Diseases of our hospital for the finding of undetectable testosterone levels during screening for osteoporosis 1 year earlier. His family history was unremarkable; by contrast, the patient’s anamnesis was remarkable for type 2 diabetes mellitus, which had been satisfactorily treated with insulin therapy during the last 10 years, and longstanding (~50 years) epilepsy, treated with phenobarbital 150 mg/day. In addition, the patient reported phlebotomies and chelation therapies for “high iron levels” 20 years earlier, which had been withdrawn for poor compliance and tolerance. Over the last 2 years, the patient had been complaining of asthenia and worsening back pain; the latter was treated with analgesics. Targeted anamnesis ascertained no libido or erections and absence of sexual intercourses dating back many years. Previous examinations included computed tomography (CT) of the spine which showed osteoarthritis and thinning of the lumbar vertebrae secondary to osteoporosis, and dual-energy X-ray absorptiometry (DXA) scan which evidenced markedly reduced BMD both in the lumbar spine (0.8 g/cm, T-score -3.6) and in the proximal femur neck (0.57 g/cm, T-score -4). Secondary hyperparathyroidism characterized by increased parathyroid hormone levels, normal calcium levels (corrected for albumin) of 9.3 mg/dL (normal range 8.5–10.5) and 25-OH vitamin D deficiency (Table 1), and undetectable testosterone levels had been ascertained. Current therapy included alendronate 70 mg/week, colecalciferol 7500 IU/week and analgesics. On physical evaluation, the patient looked pale, had no axillary or pubic hair, and markedly decreased testis volume. Further laboratory evaluations were undertaken and abnormal values are shown in Table 1. Severe hypogonadotropic hypogonadism, normochromic normocytic anemia and increased iron levels were found. No testosterone response was observed after human chorionic gonadotropin (hCG; 2000 IU i.m.) testing. Dual-energy X-ray absorptiometry scan showed an improvement in BMD only in the lumbar spine (0.84 g/cm, T-score -3.3, +3.4% vs baseline). Contrast-enhanced magnetic resonance imaging (MRI) of the pituitary gland was unremarkable. Testosterone gel 50 mg/day was started; this normalized testosterone levels (5–6 ng/mL) over months, improved libido and sexual capability, and reduced asthenia. Lipids and liver function did not change over time and anemia reversed. DXA scan performed 1 year later (during which time also bisphosphonate and vitamin D therapy were continued) showed a significant BMD increase at both lumbar (+11.4% increase vs baseline) and femur (+5.9% increase vs baseline) levels. Owing to the clinical history, the patient was referred to the Center for Iron Overload Diseases of our hospital. Markedly increased ferritin and increased percent of transferrin saturation levels were found (Table 1). Genetic testing of the HFE gene showed the homozygous p.C282Y (Cys282Tyr) mutation. The final diagnosis was type 1 HH. Measurement of liver Geriatr Gerontol Int 2011; 11: 123–126