Short-term biological variation of serum thyroid hormones concentrations in clinically healthy cats.

Thyroid disease is common in cats, but little is known about the biologic variability of serum thyroid hormone concentrations and its impact on diagnostic utility in either healthy cats or cats with thyroid disease. The purpose of this study was to determine the biological variation, index of individuality, and reference change values for thyroid hormones and thyroid-stimulating hormone (TSH) in clinically healthy cats. Serum samples for analysis of total thyroxine (T4), triiodothyronine (T3), free T4 by dialysis, and TSH were obtained weekly for 6 wk from 10 healthy cats, then frozen until single-batch analyzed. Data were evaluated for outliers, and we determined the CV within individual cats (CVI) and between individual cats (CVG) for each hormone and the variation between duplicates or analytical variation (CVA). The index of individuality and reference change values for each hormone were then calculated. Serum concentrations of total T4, free T4, T3, and TSH all showed greater variation between cats (CVG) than within cats (CVI). Total and free T4 had an intermediate index of individuality (1.1 and 1.2, respectively), suggesting that these hormones would be best evaluated by a combination of their population-based reference intervals and reference change values. Serum TSH concentrations had high index of individuality (1.8), suggesting this hormone would be best evaluated with reference change values rather than the population-based reference interval. Total T3 also had a high calculated index of individuality (1.8); however, T3 had high ratio of analytical variation (CVA) to within cat variation (CVI), so RCV could not be accurately calculated. This study demonstrates that clinically normal cats show considerable interindividual biological variation in serum thyroid hormone and TSH concentrations, whereas the intraindividual variability in hormone concentrations is much narrower. This suggests that for all serum thyroid hormones, but especially serum TSH and T3 concentrations, comparing individual cat's hormone results to a population-based reference interval may be misleading, especially in those with early or subclinical thyroid disease. Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations of T4, free T4, T3, and TSH for individual cats (ideally when healthy) and applying reference change values to subsequent measurements.

Does AMH relate to timing of menopause? Results of an Individual Patient Data meta- analysis.

CONTEXT: Anti-Müllerian hormone based (AMH) age at menopause predictions remain cumbersome due to predictive inaccuracy. OBJECTIVE: To perform an Individual Patient Data (IPD) meta-analysis, regarding AMH based menopause prediction. DATA SOURCES: A systematic literature search was performed using PubMed, Embase and Cochrane databases. STUDY SELECTION: Prospective cohort studies regarding menopause prediction using serum AMH levels were selected by consensus discussion. DATA SELECTION: Individual cases were included if experiencing a regular cycle at baseline. Exclusion criteria were hormone use and gynecological surgery. DATA SYNTHESIS: 2596 women were included, 1077 experienced menopause. A multivariable Cox regression analysis assessed time to menopause (TTM) using age and AMH. AMH predicted TTM, however, added value on top of age was poor (age alone C-statistic 84%; age + AMH HR 0.66 95% CI 0.61-0.71, C-statistic 86%). Moreover, the capacity of AMH to predict early (≤45 years) and late menopause (≥55 years) was assessed. An added effect of AMH was demonstrated for early menopause (age alone C-statistic 52%; age + AMH HR 0.33, 95% CI 0.24-0.45, C-statistic 80%). A Weibull regression model calculating individual age at menopause revealed that predictive inaccuracy remained present and increased with decreasing age at menopause. Lastly, a check of non-proportionality of the predictive effect of AMH demonstrated a reduced predictive effect with increasing age. CONCLUSION: AMH was a significant predictor of TTM and especially of time to early menopause. However, individual predictions of age at menopause demonstrated a limited precision, particularly when concerning early age at menopause, making clinical application troublesome.

Thyroid Cysts in Cats: A Retrospective Study of 40 Cases.

BACKGROUND: Thyroid cysts are rare in cats and poorly documented. OBJECTIVES: To report distinguishing clinical features and treatment responses of cats with thyroid cysts. ANIMALS: Forty client-owned cats. METHODS: Retrospective review of medical records for cats with thyroid cysts confirmed by scintigraphy, ultrasound, magnetic resonance imaging, or necropsy at 4 referral centers between 2005 and 2016. Signalment, clinical findings, diagnostic testing, treatment, and outcome were recorded. RESULTS: Cats ranged in age from 8 to 20 years with no apparent breed or sex predilection. 37 of 40 (93%) cats were hyperthyroid (duration, 1-96 months). Clinical findings included palpable neck mass (40/40, 100%), weight loss (15/40, 38%), dysphagia (8/40, 20%), decreased appetite (5/40, 13%), and dyspnea (4/40, 10%). Cysts were classified as small (≤8 cm3 ) in 16 (40%) and large (>8 cm3 ) in 24 (60%) cats. Of 25 cats treated with radioiodine, hyperthyroidism resolved in 23 (92%), whereas thyroid cysts resolved in 12 (50%). Radioiodine treatment resolved small cysts in 8 of 13 (62%) cats and large cysts in 4 of 11 (36%) cats. Eight cats, including 2 euthyroid cats, underwent thyroid-cystectomy; 3 with bilateral thyroid involvement were euthanized postoperatively for hypocalcemia. Excised cystic thyroid masses were identified as cystadenoma (4) and carcinoma (4). CONCLUSIONS AND CLINICAL IMPORTANCE: Thyroid cysts are encountered in hyperthyroid and euthyroid cats with benign and malignant thyroid tumors. Radioiodine treatment alone inconsistently resolved thyroid cysts. Thyroid-cystectomy could be considered in cats with unilateral thyroid disease or when symptomatic cysts persist despite successful radioiodine treatment of hyperthyroidism.

Efficacy of Low-dose (2 millicurie) versus Standard-dose (4 millicurie) Radioiodine Treatment for Cats with Mild-to-Moderate Hyperthyroidism.

BACKGROUND: Radioiodine (131 I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear. Treatment-induced hypothyroidism can lead to azotemia and reduced duration of survival. OBJECTIVE: To compare efficacy and short-term outcomes of low-dose 131 I versus higher, standard-dose 131 I as treatment for hyperthyroidism. ANIMALS: A total of 189 client-owned cats undergoing 131 I treatment for mild-to-moderate hyperthyroidism (serum T4 ≥ 4.0 µg/dL and <13.0 µg/dL). METHODS: Prospective, nonrandomized, cohort study comparing treatment with either low-dose (2 mCi, n = 150) or standard-dose (4 mCi, n = 39) 131 I. Serum T4 , thyroid-stimulating hormone (TSH), and creatinine concentrations were measured after 1, 3, and 6 months to determine persistent hyperthyroidism, overt hypothyroidism (low T4 , high TSH), subclinical hypothyroidism (normal T4 , high TSH), and azotemia. RESULTS: There was no significant difference in prevalence of cats with persistent hyperthyroidism between standard- and low-dose treatment groups at 3 (0% versus 5.3%; P = .34) and 6 (0% versus 3.3%; P = .51) months. Overt (18% versus 1%; P = .0005) or subclinical (46% versus 21%; P = .004) hypothyroidism was more common in cats at 6 months after standard-dose 131 I. No difference in incidence of azotemia existed between groups, but cats treated with standard-dose 131 I had higher creatinine concentrations (P < .05) and higher percent rises in creatinine (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose 131 I is safe and effective for cats with mild-to-moderate hyperthyroidism, as evidenced by a cure rate of >95% with reduced frequency of iatrogenic hypothyroidism and azotemia.

Association between changes in oestradiol and follicle-stimulating hormone levels during the menopausal transition and risk of diabetes.

AIM: To investigate the association between changes in oestradiol and follicle-stimulating hormone levels during the menopausal transition and incident diabetes. METHODS: We followed 1407 pre-menopausal women, aged 42-52 years at baseline, who experienced natural menopause, from baseline to the 12th annual follow-up visit in the Study of Women's Health Across the Nation (SWAN). Diabetes was defined based on fasting glucose level, medication use and self-report of physician diagnosis. Cox proportional hazards regression was used to evaluate the associations of incident diabetes with three components of the rate of change in hormones: the intercept (pre-menopausal levels) and two piece-wise slopes representing change during the early and late transition, respectively. RESULTS: During 15 years of follow-up, 132 women developed diabetes. After adjusting for potential confounders, a higher oestradiol intercept, but not its rate of change, was borderline significantly associated with lower risk of diabetes [hazard ratio for an interquartile range increase (75.2 pmol/L) 0.53, 95% CI 0.27-1.06]. For follicle-stimulating hormone, a greater rate of increase in the early transition, but not the intercept or late transition, was significantly associated with lower risk of diabetes [hazard ratio for an interquartile range increase (5.9 IU/L/year) 0.31, 95% CI 0.10-0.94]. CONCLUSIONS: Lower pre-menopausal oestradiol levels and a slower rate of follicle-stimulating hormone change during the early transition were associated with higher risk of developing diabetes. Given that obesity plays an important role in diabetes risk and in the levels and changes in oestradiol and follicle-stimulating hormone over the menopausal transition, weight control in earlier mid-life is important to prevent future diabetes development.

Free thyroxine concentrations by equilibrium dialysis and chemiluminescent immunoassays in 13 hypothyroid dogs positive for thyroglobulin antibody.

OBJECTIVE: To determine if concentrations of free thyroxine (FT4) measured by semi-automated chemiluminescent immunoassay (CLIA) correspond to FT4 determined by equilibrium dialysis (ED) in hypothyroid dogs positive for thyroglobulin antibody (TGA). ANIMALS: Thirteen TGA-positive dogs classified as hypothyroid based on subnormal FT4 concentrations by ED. METHODS: Qualitative assessment of canine TGA was performed using an enzyme-linked immunosorbent assay. Serum total thyroxine and total triiodothyronine concentrations were measured by radioimmunoassay. Serum FT4 concentration was determined by ED, and also by semi-automated CLIA for human FT4 (FT4h) and veterinary FT4 (FT4v). Canine thyroid stimulating hormone concentration was measured by semi-automated CLIA. RESULTS: Each dog's comprehensive thyroid profile supported a diagnosis of hypothyroidism. For detection of hypothyroidism, sensitivities of CLIA for FT4h and FT4v were 62% (95% CI, 32-85%) and 75% (95% CI, 36-96%), respectively, compared to FT4 by ED. Five of 13 (38%) dogs had FT4h and 2 of 8 (25%) dogs had FT4v concentrations by CLIA that were increased or within the reference range. Percentage of false-negative test results for FT4 by CLIA compared to ED was significantly (P < .0001 for FT4h and P < .001for FT4v) higher than the hypothesized false-negative rate of 0%. CONCLUSIONS AND CLINICAL IMPORTANCE: Caution should be exercised in screening dogs for hypothyroidism using FT4 measured by CLIA alone. Some (25-38%) TGA-positive hypothyroid dogs had FT4 concentrations determined by CLIA that did not support a diagnosis of hypothyroidism.

Bleeding patterns during the menopausal transition in the multi-ethnic Study of Women's Health Across the Nation (SWAN): a prospective cohort study.

OBJECTIVE: Previous studies describing menses duration and heaviness of flow during the menopausal transition (MT) have been short in duration and limited to white women. We estimated the frequency of and risk factors for prolonged bleeding, spotting and heavy bleeding during the MT in an ethnically diverse population. DESIGN: Prospective community-based cohort study. SETTING USA: southeastern Michigan, northern California and Los Angeles, California. POPULATION: A total of 1320 midlife women who participated in the Study of Women's Health Across the Nation (SWAN) Menstrual Calendar Substudy. Participants included African-American, white, Chinese, and Japanese women. METHODS: Women completed daily menstrual calendars from 1996 to 2006, and provided information on hormone therapy, smoking and physical activity. Annual measures included height and weight. Kaplan-Meier survival analysis and multivariable regression were used to analyse the data. MAIN OUTCOME MEASURES: Menses of 10+ days, spotting of 6+ days, heavy bleeding of 3+ days. RESULTS: At least three occurrences of menses 10+ days was reported by 77.7% (95% confidence interval [95% CI] 56.7-93.2), of 6+ days of spotting by 66.8% (95% CI 55.2-78.0) and of 3+ days of heavy bleeding by 34.5% (95% CI 30.2-39.2) of women. Menses of 10+ days, 6+ days of spotting, and 3+ days of heavy bleeding were associated with MT stage, uterine fibroids, hormone use and ethnicity. Body mass index was associated with 3+ days of heavy bleeding. CONCLUSIONS: These data provide clinicians and women with important information about the expected frequency of prolonged and heavy bleeding and spotting during the menopausal transition that may facilitate clinical decision making.

Racial/ethnic differences in hepatic steatosis in a population-based cohort of post-menopausal women: the Michigan Study of Women's Health Across the Nation.

AIMS: The prevalence of hepatic steatosis may differ between post-menopausal African-American women and non-Hispanic white women and by sex hormone binding globulin level. We examined prevalence of hepatic steatosis by race/ethnicity and associations with sex hormone binding globulin. METHODS: Participants included post-menopausal women who underwent hepatic ultrasound (n = 345) at the Michigan site of the Study of Women's Health Across the Nation, a population-based study. We examined hepatic steatosis prevalence by race/ethnicity and used logistic regression models to calculate the odds of hepatic steatosis with race/ethnicity and sex hormone binding globulin, after adjustment for age, alcohol use, waist circumference, high density lipoprotein cholesterol, triglycerides, systolic blood pressure and use of medications reported to lower intrahepatic fat. RESULTS: Fewer African-American women than non-Hispanic white women had hepatic steatosis (23 vs. 36%, P = 0.01). African-American women had lower triglyceride and low-density lipoprotein cholesterol levels, but higher blood pressure and follicle-stimulating hormone levels (P < 0.05). In the optimal-fitting multivariable models, women in the highest tertile of sex hormone binding globulin (60.2-220.3 nmol/l) had a lower odds of hepatic steatosis (odds ratio 0.43, 95% CI 0.20-0.93) compared with women in the lowest tertile of sex hormone binding globulin (10.5-40.3 nmol/l). There was an interaction between race/ethnicity and medication use whereby non-Hispanic white women using medications had three times higher odds of hepatic steatosis compared with African-American women not using medications (odds ratio 3.36, 95% CI 1.07-10.58). Interactions between race/ethnicity and other variables, including sex hormone levels, were not significant. CONCLUSIONS: Hepatic steatosis on ultrasound may be more common in post-menopausal non-Hispanic white women than African-American women and was associated with lower levels of sex hormone binding globulin.

Resting energy expenditure per lean body mass determined by indirect calorimetry and bioelectrical impedance analysis in cats.

BACKGROUND: Resting energy expenditure (REE) approximates ≥60% of daily energy expenditure (DEE). Accurate REE determination could facilitate sequential comparisons among patients and diseases if normalized against lean body mass (LBM). OBJECTIVE: (1) Validate open-flow indirect calorimetry (IC) system and multifrequency bioelectrical impedance analysis (MF-BIA) to determine REE and LBM, respectively, in healthy nonsedated cats of varied body conditions; (2) normalize REE against LBM. ANIMALS: Fifty-seven adult neutered domestic short-haired cats with stable BW. METHODS: Continuous (45-min) IC-measurements determined least observed metabolism REE. Cage gas flow regulated with mass flow controllers was verified using nitrogen dilution; span gases calibrated gas measurements. Respiratory quotient accuracy was verified using alcohol combustion. IC-REE was compared to DEE, determined using doubly labeled water. MF-BIA LBM was validated against criterion references (deuterium, sodium bromide). Intra- and interassay variation was determined for IC and MF-BIA. RESULTS: Mean IC-REE (175 ± 38.7 kcal; 1.5-14% intra- and interassay CV%) represented 61 ± 14.3% of DEE. Best MF-BIA measurements were collected in sternal recumbency and with electrodes in neck-tail configuration. MF-BIA LBM was not significantly different from criterion references and generated LBM interassay CV% of 6.6-10.1%. Over- and underconditioned cats had significantly (P ≤ .05) lower and higher IC-REE (kcal/kg) respectively, compared with normal-conditioned cats. However, differences resolved with REE/LBM (approximating 53 ± 10.3 kcal/LBM [kg]). CONCLUSIONS AND CLINICAL IMPORTANCE: IC and MF-BIA validated herein reasonably estimate REE and LBM in cats. REE/LBM(kg) may permit comparison of energy utilization in sequential studies or among different cats.

The influence of reproductive hormones on brain function in the menopausal transition.

Reproductive hormones have long been thought to have a significant impact on brain function in humans. Estrogens, progestins and androgens have all been shown to have effects on nerve growth and function in vitro. The neurofunctional domains of cognition, mood and sleep are now receiving increased study to determine both the relationship of endogenous sex steroids through the menopausal transition and the effect of menopausal hormone therapy on these complex functions. All three domains are the source of frequent concern in midlife women, but the relative contribution of ovarian versus somatic aging is only now being untangled. Cognitive function has been most extensively studied, with mixed results in both observational studies and clinical trials, largely due to the remarkably complex aspects of human cognition requiring extensive and targeted testing of specific components. Both mood and sleep disorders have been associated with the menopausal transition, but observed effects appear modest. To date, clinical trial data are insufficient to support the use of hormone therapy specifically for the prevention or treatment of cognitive, mood or sleep disorders in midlife women.

Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging.

BACKGROUND: In this study, levels and rates of change in total testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were related to chronological age and to the final menstrual period (FMP) as an indicator of ovarian aging. METHODS: Data were annually acquired over a 15-year period in 629 women of the Michigan Bone Health and Metabolism Study cohort. Data were censored for hormone therapy use. Endogenous androgen patterns over time were described with stochastic processes and bootstrapping. RESULTS: With ovarian aging, T levels rose from a mean of 18 ng/dl commencing 10 years prior to the FMP to 27 ng/dl at the FMP. Over the 20-year period encompassing the FMP, modeled mean SHBG levels changed from 58 to 34 nM and the FAI ratio increased from 1.6 to 2.9 in a non-linear manner. With chronological aging, total T levels increased (P < 0.0001) from 43 to 50 years, but not thereafter. SHBG declined steadily with age with a modestly greater rate of change between 49 and 54 years. The FAI increased from 1.3 to 2.5 from 34 to 58 years. CONCLUSIONS: T increased from approximately age 40 until the FMP whereas SHBG had rate of change patterns reflecting both chronological and ovarian aging components. These data provide new insight into the endogenous androgen patterns at mid-life.

Factors related to declining luteal function in women during the menopausal transition.

CONTEXT: Reproductive hormones are incompletely characterized during the menopause transition (MT). HYPOTHESIS: Increased anovulation and decreased progesterone accompany progress through the MT. DESIGN: The Daily Hormone Study (DHS) of the Study of Women's Health Across the Nation (SWAN) included 848 women aged 43-53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr. MAIN OUTCOME MEASURES: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables. RESULTS: Ovulatory-appearing cycles declined from 80.9% at baseline to 64.7% by the third assessment (H3). Cycles presumed anovulatory and not ending with bleeding by 50 d (anovulatory/nonbleeding) increased from 8.4 to 24% by H3 and were associated with progress to early perimenopause [odds ratio (OR) = 2.66; confidence interval (CI) = 1.17-6.04] or late perimenopause (OR = 56.21; CI = 18.79-168.12; P < 0.0001), African-American ethnicity (OR = 1.91; CI = 1.06-3.43), and less than high school education (OR = 3.51; CI = 1.62-7.62). Anovulatory cycles ending with bleeding remained at about 10% from baseline to H3; compared with ovulatory cycles, they were associated with obesity (OR = 4.68; CI = 1.33-16.52) and more than high school education (OR = 2.12; CI = 1.22-3.69; P = 0.02). Serum estradiol in both the highest and lowest categories was associated with anovulatory/nonbleeding collections. Pregnanediol glucuronide decreased 6.6% for each year on study. Insulin sensitivity measures did not relate strongly to menstrual cycle hormones. CONCLUSIONS: Anovulation without bleeding represents progression of the MT. A small but detectable decrease in luteal progesterone excretion occurs as women progress through the MT.

The effects of S-adenosylmethionine on clinical pathology and redox potential in the red blood cell, liver, and bile of clinically normal cats.

S-adenosylmethionine (SAMe), an important hepatic metabolite and glutathione (GSH) donor, has been studied mechanistically in vitro, in humans with clinical liver disease, and in experimental animal models of liver disease. Collective findings encourage its therapeutic use in necroinflammatory and cholestatic liver disorders. A chronic longitudinal study (pre- and posttreatment parameters compared) was undertaken with 15 clinically healthy cats given a stable 1,4-butanedisulfonate (S'S isomer) SAMe salt (enteric coated tablets providing 180 mg SAMe), dosage 48 mg/kg PO q24h, on an empty stomach for 113 days. Routine physical and clinicopathologic assessments, red blood cell (RBC) osmotic fragility, liver function and histology, hepatic concentrations of reduced GSH (RGSH) and its oxidized disulfide form (GSSG), protein, glycogen, and deoxyribonucleic acid, GSH concentrations in RBCs, total bile acids in serum and bile, oxidative membrane products (TBARS) in RBCs and liver, and plasma SAMe concentrations were evaluated. SAMe administered PO significantly increased plasma SAMe concentrations, and peak concentrations usually occurred 2-4 hours after dosing. Chronic SAMe administration did not change peak or cumulative plasma SAMe concentrations and did not [corrected] cause overt signs of toxicity. A positive influence on RBC and hepatic redox status (RBC TBARS reduced 21.1% [P < .002], liver GSH increased 35% [P < .002], liver RGSH: GSSG ratio increased 69% [P < .03]) and improved RBC resilience to osmotic challenge (P < .03) were observed. Results prove that this SAMe PO product is enterically available and suggest that it imparts biologic effects that might be useful for attenuating systemic or hepatic oxidant challenge.

Electroejaculation and assisted reproductive technologies in the treatment of anejaculatory infertility.

OBJECTIVE: To determine the efficacy of electroejaculation in combination with assisted reproductive technology (ART). DESIGN: Case series. SETTING: University fertility program. PATIENT(S): One hundred twenty-one consecutive couples seeking treatment of anejaculatory infertility. INTERVENTION(S): Electroejaculation with IUI, or gamete intrafallopian transfer or IVF. MAIN OUTCOME MEASURE(S): Pregnancy and pregnancy outcome. RESULT(S): Fifty-two couples became pregnant (43%), 39 by IUI alone (32.2%). Cycle fecundity for IUI was 8.7%. No difference in cycle fecundity was seen among ovarian stimulation protocols (clomiphene citrate, 7.6%, hMG, 13.2%, and natural cycle, 11.2%). Pregnancy was unlikely when the inseminated motile sperm count was <4 million. Female management protocol and etiology of anejaculation did not affect results. Patients undergoing IVF had higher cycle fecundity (37.2%) than did those undergoing IUI. The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively. CONCLUSION(S): Electroejaculation with stepwise application of ART is effective in treating anejaculatory infertility. Intrauterine insemination with the least expensive monitoring protocol should be used for most couples, because use of more expensive monitoring did not improve results. It is cost-effective to bypass IUI and proceed directly to IVF in men who require anesthesia for electroejaculation and in those with a total inseminated motile sperm count < 4 million.

Dynamics of bioactive follicle-stimulating hormone secretion in women with polycystic ovary syndrome: effects of estradiol and progesterone.

OBJECTIVE: To determine the nature of bioactive FSH secretion in anovulatory women with polycystic ovary syndrome (PCOS) and its modulation by luteal levels of E2 and P. DESIGN: Interventional and observational study. SETTING: Academic clinical research center. PATIENT(S): Five patients with PCOS. INTERVENTION(S): Treatment for 21 days with luteal levels of E2 and P. MAIN OUTCOME MEASURES: Serum levels of immunoreactive LH, immunoreactive FSH, bioreactive FSH, and the FSH isoform distribution pattern. Blood was sampled frequently and GnRH testing was done on day 0 (before treatment), days 10 and 20 (during treatment), and day 28 (7 days after treatment). RESULT(S): Treatment with E2 and P suppressed circulating immunoreactive LH and immunoreactive FSH but not bioreactive FSH. Anovulatory women with PCOS showed a predominantly acidic pattern of FSH isoform distribution. Treatment with E2 and P shifted the distribution profile of FSH isoforms to the less acidic. After cessation of E2-P treatment, FSH reverted to its pretreatment pattern of distribution. CONCLUSION(S): Resumption of follicular growth after luteal replacement of E2 and P in anovulatory women with PCOS may be related to the reduction in the elevated LH/FSH ratio and accompanying changes in the FSH signal.

Idiopathic hypercalcemia in cats.

Unexplained hypercalcemia has been increasingly recognized in cats since 1990. In some instances, hypercalcemia has been associated with calcium oxalate urolithiasis, and some affected cats have been fed acidifying diets. We studied the laboratory findings, clinical course, and treatment of 20 cats with idiopathic hypercalcemia. Eight (40%) of the cats were longhaired and all 14 cats for which adequate dietary history was available had been fed acidifying diets. Clinical signs included vomiting (6 cats), weight loss (4 cats), dysuria (4 cats), anorexia (3 cats), and inappropriate urinations (3 cats). Hypercalcemia was mild to moderate in severity. and serum parathyroid hormone concentrations were normal or low. Serum concentrations of phosphorus, parathyroid hormone-related peptide, 25-hydroxycholecalciferol, and calcitriol were within the reference range in most cats. Diseases commonly associated with hypercalcemia (eg, neoplasia, primary hyperparathyroidism) were not identified despite thorough medical evaluations and long-term clinical follow-up. Azotemia either did not develop (10 cats) or developed after the onset of hypercalcemia (3 cats), suggesting that renal failure was not the cause of hypercalcemia in affected cats. Seven of 20 cats (35%) had urolithiasis, and in 2 cats uroliths were composed of calcium oxalate. Subtotal parathyroidectomy in 2 cats and dietary modification in 11 cats did not result in resolution of hypercalcemia. Treatment with prednisone resulted in complete resolution of hypercalcemia in 4 cats.

Monoclonal immunoglobulin G cryoglobulinemia and multiple myeloma in a domestic shorthair cat.

A 13-year-old castrated domestic shorthair cat was examined because of fever, anorexia, and dermatologic lesions. Crusting, erythema, and well-demarcated purple discoloration of the foot pads and the tips of the pinnae, nose, and tail were seen. A white flocculent precipitate was detected in cooled serum. This precipitate dissolved upon rewarming, consistent with a cryoglobulin. Hypercalcemia, high alanine and aspartate aminotransferase activities, thrombocytopenia, and a monoclonal IgG gammopathy were found. Numerous hepatic nodules were detected by means of abdominal ultrasonography. Cytologic evaluation of fine-needle aspirates of the liver and spleen revealed numerous plasma cells, and evaluation of a bone marrow aspirate revealed plasmacytosis. A diagnosis of multiple myeloma and monoclonal IgG cryoglobulinemia was made, and the cat was euthanatized.