We examined core body temperature (CBT) of urocortin 1 (UCN1) and corticotropin releasing factor (CRF) knockout (KO) mice exposed to 4°C for 2 h. UCN1KO mice showed higher average CBT during cold exposure as compared to WT. The CBT of male and female WT mice dropped significantly to34.1 ± 2.4and34.9 ± 3.1 C at 4°C, respectively. In contrast, the CBT of male and female UCN1KO mice dropped only slightly after 2 h at 4°C to36.8 ± 0.7and38.1 ± 0.5 C, respectively. WT female and male UCN1KO mice showed significant acclimatization to cold; however, female UCN1KO mice did not show such a significant acclimatization. CRFKO mice showed a dramatic decline in CBT from38.2 ± 0.4at 22°C to26.1 ± 9.8at 4°C for 2 h. The CRF/UCN1 double KO (dKO) mice dropped their CBT to32.5 ± 4.0after 2 h exposure to 4°C. Dexamethasone treatment prevented the decline in CBT of the CRFKO and the dKO mice. Taken together, the data suggest a novel role for UCN1 in thermoregulation. The role of CRF is likely secondary to adrenal glucocorticoids, which have an important regulatory role on carbohydrate, fat, and protein metabolism.

MAPK phosphatase 1 (MKP‐1), a member of the dual‐specificity phosphatases, inactivate MAPKs via dephosphorylation of ERK, p38 and JNK. Whether MKP‐1 plays a role in PTH and PTHrP anabolic action in bone is yet to be investigated. Our previous study demonstrated a decrease in ERK‐MAPK and cyclin D1 and an increase in MKP‐1 expression in differentiated osteoblasts following PTH/PTHrP induction both in vitro and in vivo. To investigate the effect of MKP‐1 deletion in PTH1R anabolic action, primary calvarial osteoblasts were isolated from neonatal or 10‐week old MKP‐1 knock out (KO) and wild type (WT) mice via sequential collagenase digestion. The cells were differentiated with ascorbic acid (100μg/ml) and β‐glycerophosphate (5mM) and harvested between 7 to 21 days. Von Kossa staining at day 14 showed decreased mineralization in MKP‐1 KO osteoblasts compared to WT. In contrast to WT cells incubation of MKP‐1 KO osteoblasts with 100nM PTHrP had no effects on pERK or cyclin D1 expression. MicroCT analysis of mid‐diaphyses of tibiae and femora from 2 week old MKP‐1 KO mice showed decreased bone mineral density (BMD), bone mineral content (BMC) and tissue mineral content (TMC) compared to WT bone. Taken together, these results show that MKP‐1 may be important for PTH/PTHrP anabolic action in osteoblasts and play a role in the maintenance of bone mass.(Supported by NIH R03 DE018245‐01 and R01DK53904)

We are reporting a case of SIADH hyponatremia and pan-hypopituitarism in an otherwise stable appearing non-functional pituitary macroadenoma on MRI that suddenly developed apoplexy. Patient is a 52-year-old hispanic male with a history of a pituitary adenoma diagnosed initially on 06/2017 during MRI head for chronic headaches. MRI Pituitary on 07/2018 showed “well-circumscribed lesion” measuring approximately 12.7 x 14.8 x 13.4 mm in AP. Hormonal work up was normal in 06/2017, 01/2018, and 07/2018. In 07/2018 labs showed: IGF-1 247 ng/mL (65–222), ACTH 28 pg/mL (7–69), random cortisol 8.58 microg/dL (3.09–22.4), TSH 2.3 mIU/mL (0.4–5.5), fT4 1.06 ng/dL (0.8–1.8), LH 4.6 mIU/mL (0.98–79.7), FSH 6.2 MIU/mL (1–18), prolactin 2.92 ng/mL (2.1–24), and testosterone 310 ng/dL (87–814). Oral glucose tolerance test was done and showed: GH was 0.34 ng/mL at baseline and 1.01 ng/mL after 75 g oral glucose (equivocal result). Repeat IgF1 was normal after that. Subsequently, patient was admitted on 09/24/2018 with severe headaches, nausea, vomiting, polyuria, and polydipsia. He was hypotensive and tachycardic and was found to be hyponatremic with a Na of 124, lowest at 119 where hypertonic saline was given at that point. Urine output was 1.5 L in 24 hours while he was on an 0.8 L fluid restriction, and then 6 L the following day while he was on 1.5 L fluid restriction, serum osmolality was 251, urine osmolality was 1003, urine specific gravity was >1.030. Nephrology agreed to the diagnosis of SIADH. Blood work on 09/24 showed: random cortisol 0.67 microg/dL, TSH 0.19 mIU/mL, free T4: 0.63 ng/dL, ACTH 11 pg/mL, LH 2.4 mIU/mL, FSH 4.7 MIU/mL, testosterone 13 ng/dl. Patient was started on Levothyroxine 125 mcg and hydrocortisone stress dose. MRI brain was done and showed a pituitary macro-adenoma, measuring approximately 14 x 11 x 11 mm with no significant change in size since 6/30/2017, without optic nerve compression, no hemorrhage was mentioned. Work up for other causes of panhypopituitarism, i.e. hemochromatosis was done and was negative: Ferritin: 258 ng/mL (22–322). CT abdomen and pelvis was also done and showed normal adrenal glands. We thought about granulomatous infiltrative diseases like sarcoidosis since 1–25 (OH) vitamin D was high at 120 pg/mL (19.9–79.3). CT neck and chest was done but was negative for sarcoidosis or lymphadenopathy. Patient was seen outpatient by neurosurgery in 1/2019 and a repeat MRI was done which reported resolution of cystic and blood material from a pituitary adenoma, and per neurosurgery there is resolution of a pituitary cystic adenoma with apoplexy that now looks like a partial empty sella. Patient currently continues to be pan-hypopituitary requiring hydrocortisone, levothyroxine and testosterone replacement. SIADH has resolved. An otherwise non-functioning stable pituitary macroadenoma on MRI, can suddenly present as symptomatic apoplexy with SIADH and pan-hypopituitarism.

Introduction: Levothyroxine (LT4) is the mainstay of treating hypothyroidism patients. Increased levothyroxine requirements are expected after bariatric surgery and small bowel diseases. There have been studies showing treatment of resistant hypothyroidism following bariatric surgery with soft gel or liquid form of LT4. Here we report a case of biliopancreatic diversion in which thyroid hormone replacement could not be done with LT4. However, treatment with Liothyronine (LT3) was successful. The Case: 57 year old Caucasian male with history of gastric bypass surgery for morbid obesity in 2009, chronic pain, cauda equine syndrome, iron deficiency anemia due to poor gastric absorption after gastric bypass surgery, on IV iron, and post ablative hypothyroidism since 1993 who presented to the VA endocrinology clinic for hypothyroidism. He had been controlled on thyroid replacement with LT4 tablets since 1993 up until he had biliopancreatic diversion with duodenal switch in Oct 2009. He was seen at the VA endocrinology clinic first in March 2016. Outside records indicated that TSH was high between 2009-2016. He claimed compliance on thyroxine PO at 300 mcg daily. From March 2016 until May 2018, LT4 dose was increased gradually to 875 mcg in am with water. In March 2018 TSH was 44.95 µIU/ml, free T4 0.92 ng/dL, and total T3 62.39 ng/dL and the albumin level was 4.1 g/dL. TSH level decreased to 17 µIU/mL in June 2018 after levothyroxine dose was increased to 875 mcg in May 2018. Since liquid or soft gel forms are non-formulary at the VA, he was treated with Liothyronine PO at 50 mcg daily. TSH level in October 2018 was 0.05 µIU/mL, fT4 was 1.77 ng/dL, and total T3 146.4 ng/dL. Conclusion: Biliopancreatic diversion can severely affect LT4 absorption. LT3 may have better bioavailability than LT4 tablets after bariatric surgery.