Diagnostic Threshold for Postoperative Secondary Adrenal Insufficiency After Transsphenoidal Resection of Pituitary Adenomas

Abstract Transsphenoidal surgery (TSS) is the first line treatment for pituitary adenomas. A well-known complication of TSS is secondary adrenal insufficiency with a reported risk of 4-9% after TSS. Currently, glucocorticoid replacement is recommended if postoperative AM cortisol is < 3 ug/dL. Postoperative adrenal insufficiency is ruled out if AM cortisol is > 15 ug/dL. However, further evaluation of the adrenal axis with ACTH stimulation test is recommended for intermediate cortisol levels 3-15 ug/dL. Other studies have proposed postoperative cortisol threshold of < 4-14 ug/dL for glucocorticoid replacement. Retrospective analysis of all patients undergoing TSS at a tertiary center from January 2013 through April 2016 was performed. ACTH producing adenomas (Cushing’s disease) were excluded. Of the 97 patients included, 17.5% (n=17) had secondary adrenal insufficiency requiring glucocorticoid replacement at 1 year post operatively. Mean age at presentation was 56 ± 16 years and 52% were female. Mean adenoma size was 25.3 ± 11.3 mm. Factors associated with adrenal insufficiency at 1 year post operatively were preoperative secondary adrenal insufficiency (AM cortisol 4.5 ± 1.9 vs 11.0 ± 1.0 µg/dL; p = 0.03), and preoperative adenoma contact with optic chiasm (15.7% vs 2.1%; p = 0.01). Day 1-7 postoperative cortisol was lower in the group with adrenal insufficiency at 1 year (5.6 µg/dL (IQR 1.9-11.5) vs 19.8 µg/dL (IQR 12.75-43.2); p=0.02). Age, gender, adenoma size, and cavernous sinus involvement were not associated with adrenal insufficiency at 1 year. A day 1-7 postoperative cortisol concentration of ≥8.0 µg/dL had a sensitivity of 75% and specificity of 92% in predicting adrenal insufficiency at 1 year. In patients with secondary adrenal insufficiency at 1 year (n=17), there was a higher frequency of concomitant loss of other pituitary hormone function at 1 year: secondary hypothyroidism 82% (n=14), secondary hypogonadism 70.6% (n=12) and diabetes insipidus 17.7% (n=3). A lower postoperative cortisol threshold of 8 µg/dL can be adopted for glucocorticoid replacement on discharge after TSS.

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MON-304 Prolactin as a Surrogate Marker to Predict Long Term Postoperative Hypopituitarism After Transsphenoidal Resection of Pituitary Adenomas

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1282 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Massiell German ◽

Devaprabu Abraham ◽

William Couldwell ◽

Debra L Simmons ◽

Anu Sharma

Keyword(s):

Adrenal Insufficiency ◽

Pituitary Adenomas ◽

Surrogate Marker ◽

Older Age ◽

Pituitary Function ◽

Secondary Adrenal Insufficiency ◽

Secondary Hypothyroidism ◽

Tertiary Center

Abstract Transsphenoidal surgery (TSS) is the first line treatment for pituitary adenoma. A well-known complication of TSS is hypopituitarism with a reported risk of 5-25% after resection of pituitary adenomas. A decrease in postoperative prolactin concentration was shown to be associated with postoperative hypopituitarism in a previous report. We hypothesized that in addition to clinical factors (preoperative hypofunction and adenoma size), biochemical factors (change in prolactin concentration and immediate post-operative hypofunction) can aid in predicting long term hypopituitarism as defined as ≥1 biochemically confirmed hypofunctioning pituitary axes 3 years after resection. A retrospective analysis of all patients undergoing TSS for both functioning and non-functioning pituitary adenomas at a tertiary center from January 2013 through December 2015 was performed. Prolactinomas were excluded. Of the 75 patients included, 21.3% (n=16) had at least one pituitary axis requiring replacement at 3 years post operatively. Mean age at presentation was 55 ± 16 years, 55% were female and 81% were Caucasian. Mean adenoma size was no different between normal pituitary function and hypopituitary groups (24.0 ± 11.9 mm versus 25.3 ± 10, p=0.7). Factors associated with long term hypopituitarism were older age (mean age 64 ± 4 years versus 53 ± 2 years, p = 0.02), preoperative secondary adrenal insufficiency (AM cortisol 6.4 ± 3.7 vs 12.0 ± 6.5 µg/dL; p = 0.03), preoperative secondary hypothyroidism (0.8 ± 0.2 vs 12.0 ± 6.5 ng/dL; p < 0.01), low immediate postoperative cortisol (5.3±3.1 vs 26.1±18.3 µg/d; p<0.01), and persistence of adrenal insufficiency (10.7% vs 2.7%; p<0.01) and secondary hypothyroidism (13.3% vs 5.3%; p<0.01) at 3 months. Change in prolactin concentration from preoperative to postoperative day 1-7 was not significantly different between groups (p=0.09) due to the higher variability in the hypopituitary group (median 0.2 ng/mL, IQR -0.5 - 0.8 ng/mL) compared to the normal pituitary function group (median 0.7 ng/mL, IQR 0.5-0.8 ng/mL). Adenoma size, optic chiasm and cavernous sinus involvement were not associated with long term hypopituitarism. In patients who developed postoperative hypopituitarism, there was a higher frequency of adenoma persistence or recurrence (20% vs 47%). There was a high rate of patients lost to follow up (56%). Older age, the presence of preoperative secondary adrenal insufficiency and hypothyroidism, and low day 1-7 postoperative cortisol concentration are factors that can be used to deem a patient high risk for future hypopituitarism. These patients should have close follow up with continued screening postoperatively. Contrary to prior reports, adenoma size and parasellar involvement were not associated which may be suggestive of surgical expertise. Prolactin concentrations proved not to be a good surrogate marker to predict long term hypopituitarism.

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The Effect of Secondary Hypothyroidism and Secondary Hypogonadism on the ACTH Stimulation Test

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2012.07.043 ◽

2012 ◽

Vol 36 (5) ◽

pp. S9

Author(s):

Churn-Ern Yip ◽

Fatima Imran ◽

Sam Stewart ◽

Arati Mokashi ◽

Mohammed Al-Otaibi ◽

...

Keyword(s):

Stimulation Test ◽

Acth Stimulation Test ◽

Acth Stimulation ◽

Secondary Hypothyroidism ◽

Secondary Hypogonadism

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Secondary Adrenal Insufficiency Is Associated with Poor Survival Outcomes in Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.5631.5631 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5631-5631

Author(s):

Seo-Yeon Ahn ◽

Sung-Hoon Jung ◽

Hee Kyung Kim ◽

Ho-Cheol Kang ◽

Deok-Hwan Yang ◽

...

Keyword(s):

Multiple Myeloma ◽

Adrenal Insufficiency ◽

Clinical Significance ◽

Predictive Factors ◽

Conflicts Of Interest ◽

Hospitalized Patients ◽

Survival Outcomes ◽

Secondary Adrenal Insufficiency ◽

Poor Survival ◽

Acth Stimulation

Abstract Background: Glucocorticoids has been a backbone of various treatment regimens for multiple myeloma (MM). The repeated and chronic use of high doses of glucocorticoids is associated with development of secondary adrenal insufficiency (AI), and AI could be a major problem in critically-ill patients. However, there has been no specialized data about incidence and clinical significance of secondary AI in hospitalized patients with MM. Purpose: The objective of this retrospective study is to evaluate incidence, predictive factors, and clinical significance of secondary AI in hospitalized patients with MM. Methods: We retrospectively evaluated medical records of MM patients who were hospitalized in Chonnam National University Hwasun Hospital, South Korea from December 2014 to December 2015. The definite AI was diagnosed when the peak cortisol concentration was less than < 500 nmol/L (18 mcg/dL) after ACTH administration. Results: Between December 2014 and December 2015, 77 patients were hospitalized, and 58 underwent rapid ACTH stimulation test. The most frequent cause of hospitalization was infection (70.7%), followed by weakness (24.1%), and the others (5.3%). The definite AI was confirmed in 19 patients (32.7%). To evaluate the predictive factors of AI, all variables including clinical characteristics, laboratory results, cumulative steroid dose, and treatment duration at hospitalization were analyzed, but there were no significant predictors for AI. In addition, the patients with AI had a significantly poor survival outcomes compared to those without AI (the median overall survival of 42.3 months vs. 82.7 months; P = 0.037) (Figure 1). Conclusions: This study showed that the secondary AI is not a rare condition among hospitalized patients with MM, and there was no specific predictable symptoms or signs. In addition, development of AI in the treatment period is associated with a poor prognosis. This study suggests that evaluation of AI is routinely needed in hospitalized patients with MM. Disclosures No relevant conflicts of interest to declare.

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Reduced epinephrine reserve in response to insulin-induced hypoglycemia in patients with pituitary adenoma

Acta Endocrinologica ◽

10.1530/eje-07-0176 ◽

2007 ◽

Vol 157 (3) ◽

pp. 265-270 ◽

Cited By ~ 2

Author(s):

Shinya Morita ◽

Michio Otsuki ◽

Maki Izumi ◽

Nobuyuki Asanuma ◽

Shuichi Izumoto ◽

...

Keyword(s):

Pituitary Adenoma ◽

Adrenal Insufficiency ◽

Serum Cortisol ◽

Tolerance Test ◽

Secondary Adrenal Insufficiency ◽

Counterregulatory Hormones ◽

Insulin Tolerance ◽

Secondary Hypothyroidism ◽

Severe Impairment ◽

Plasma Gh

Objective: Hypoglycemia induces rapid secretion of counterregulatory hormones such as catecholamine, glucagon, cortisol, and GH. Insulin-induced hypoglycemia is used for evaluating GH–IGF-I and ACTH–adrenal axes in patients with pituitary disorders. The aim of this study was to determine whether the response of catecholamine secretion to hypoglycemia is disrupted in patients with pituitary adenoma. Methods: The study population comprised 23 patients with pituitary adenoma (non-functioning adenoma or prolactinoma). An insulin tolerance test was performed and serum catecholamines as well as plasma GH and serum cortisol were measured. Results: The study patients showed diminished response of plasma epinephrine to insulin-induced hypoglycemia. With the cutoff level of peak epinephrine for defining severe impairment set at 400 pg/ml, more patients with secondary adrenal insufficiency showed severe impairment of the epinephrine response than did those without it. Peak epinephrine levels to insulin-induced hypoglycemia were significantly correlated with peak cortisol levels. In patients with secondary hypothyroidism, secondary hypogonadism, GH deficiency, or diabetes insipidus, the prevalence of severe impairment of the epinephrine response was similar to that in patients without these deficiencies. Conclusions: Impaired epinephrine secretion in response to insulin-induced hypoglycemia was frequently observed in patients with pituitary adenoma. This disorder was especially severe in patients with secondary adrenal insufficiency.

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Two Cases of Pembrolizumab-Induced Secondary Adrenal Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.328 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A162-A162

Author(s):

Akinori Kanzaki ◽

Taiichirou Otsuki ◽

Tohru Arii ◽

Hidenori Koyama ◽

Satoru Katayama

Keyword(s):

Adrenal Insufficiency ◽

Stage Iv ◽

Japanese Patients ◽

Pituitary Cell ◽

Hla Typing ◽

Test Results ◽

Secondary Adrenal Insufficiency ◽

Acth Stimulation ◽

Cell Antibody ◽

Anterior Pituitary Function

Abstract Title: Two cases of pembrolizumab-induced secondary adrenal insufficiency Background: Although few cases regarding pembrolizumab-induced secondary adrenal insufficiency were reported, it has recently been published that significantly higher prevalence of human leucocyte antigen (HLA)-DR15, B52, and Cw12 was revealed in 11 Japanese patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency as compared with healthy controls and DR15 might be a predictive marker. This is based on the evidence that DR15 has associations with IL-17-mediated autoimmune disease such as Hashimoto’s thyroiditis, and that anti-programmed death 1 (PD-1) inhibitors activate the Th1 and Th17 pathways. We here introduce two Japanese patients with pembrolizumab-induced secondary adrenal insufficiency from a viewpoint of their HLA typing test results. Clinical Case: Case 1. A 52-year old male diagnosed with stage IV lung cancer (squamous non-small cell lung cancer) was treated with chemotherapy consisting of carboplatin, nab-paclitaxel, and pembrolizumab. Six days after the fourth cycle of pembrolizumab, he suffered from hypoglycemia and hyponatremia. Endocrinological examination findings showed ACTH and cortisol deficiency throughout the day, after which a diagnosis of secondary adrenal insufficiency was made based on no response shown in insulin tolerance, anterior pituitary function, and rapid ACTH stimulation tests. Pituitary cell antibody-1 was negative, and no evidence of a swollen/atrophied pituitary gland or space occupying lesion was observed in magnetic resonance imaging (MRI) results. Furthermore, Hashimoto’s thyroiditis was suspected based on anti-thyroid peroxidase antibody positivity. HLA typing test results highly corresponded with the reported results (A24, B52, Cw12, DR4, DR15). Case 2. A 70-year old male was treated with pembrolizumab for recurrence of lung squamous cell carcinoma (stage IV). Two weeks after completion of five cycles, severe diarrhea occurred, suspected to be a side effect of pembrolizumab, which was relieved with temporary use of prednisolone. However, diarrhea recured accompanied with a high fever, eosinophilia, and acute hyponatremia. Based on results showing deficiency of ACTH and cortisol, adrenal insufficiency was suspected. Anterior pituitary function and rapid ACTH stimulation test results supported that diagnosis, while pituitary cell antibody-1 was negative and MRI findings were not remarkable. Notably, completely different HLA typing test results were observed. Conclusion: Similar to the previous report, HLA-A24, B52, Cw12, DR4, and DR15 were found in case 1, whereas all subtypes including HLA-DR15 were lacking in case 2. We think that it should not be given low priority for cases lacking DR15 and the possibility of an association with IL-17 in such cases is required in feature study.

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Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases

Acta Endocrinologica ◽

10.1530/eje.0.1480609 ◽

2003 ◽

pp. 609-617 ◽

Cited By ~ 86

Author(s):

S Diederich ◽

NF Franzen ◽

V Bahr ◽

W Oelkers

Keyword(s):

Adrenal Insufficiency ◽

Antidiuretic Hormone ◽

Hospital Admissions ◽

Clinical Signs ◽

University Hospital ◽

Pituitary Hormone ◽

Stressful Situation ◽

Secondary Adrenal Insufficiency ◽

Severe Hyponatremia ◽

Underlying Disorder

OBJECTIVE: Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. METHODS: In a retrospective study we screened the files of 185 patients with severe hyponatremia (<130 mmol/l) that had been seen in one endocrinological unit of a university hospital between 1981 and 2001 in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency. RESULTS: In 139 cases it was possible to clearly ascribe the patients to the pathophysiological groups of (i) primary sodium deficiency, (ii) edematous disorders, and (iii) normovolemic disorders including the "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH). Twenty-eight patients with severe "normovolemic hyponatremia" (serum sodium: 116+/-7 mmol/l, mean+/-s.d.) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function. In 25 cases of this group hypopituitarism (mostly due to empty sella, Sheehan's syndrome and pituitary tumors) had not been recognized previously, and in 12 cases recurrent hyponatremia during previous hospital admissions (up to four times) could be documented. The mean age of these patients (21 women, seven men) was 68 Years. The most frequently occurring clinical signs were missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in the men. Frequent symptoms like nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 patients with SIADH. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439 nmol/l (mean+/-s.d.: 157+/-123), while in 30 other severely hyponatremic patients it ranged from 274 to 1732 nmol/l (732+/-351 nmol/l). In most patients with hyponatremic hypopituitarism, plasma antidiuretic hormone levels were inappropriately high, probably due to a failure of endogenous cortisol to suppress the hormone in a stressful situation. All patients recovered after low-dose hydrocortisone substitution. Most patients had other pituitary hormone deficiencies and were appropriately substituted subsequently. CONCLUSIONS: Hypopituitarism including secondary adrenal insufficiency seems to be a frequently overlooked cause of severe hyponatremia. A high level of suspicion is the best way to recognize the underlying disorder. Treatment with hydrocortisone is very effective.

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ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy

Acta Endocrinologica ◽

10.1530/eje-21-0462 ◽

2021 ◽

Vol 185 (3) ◽

pp. G1-G33

Author(s):

A Luger ◽

L H A Broersen ◽

N R Biermasz ◽

B M K Biller ◽

M Buchfelder ◽

...

Keyword(s):

Pregnant Women ◽

Pituitary Adenomas ◽

Radiation Treatment ◽

Therapeutic Option ◽

Safety Data ◽

Premenopausal Women ◽

Optic Chiasm ◽

Pituitary Hormone ◽

Hormone Substitution ◽

Endocrine Activity

Pregnancies are rare in women with pituitary adenomas, which may relate to hormone excess from secretory subtypes such as prolactinomas or corticotroph adenomas. Decreased fertility may also result from pituitary hormone deficiencies due to compression of the gland by large tumours and/or surgical or radiation treatment of the lesion. Counselling premenopausal women with pituitary adenomas about their chance of conceiving spontaneously or with assisted reproductive technology, and the optimal pre-conception treatment, should start at the time of initial diagnosis. The normal physiological changes during pregnancy need to be considered when interpreting endocrine tests in women with pituitary adenomas. Dose adjustments in hormone substitution therapies may be needed across the trimesters. When medical therapy is used for pituitary hormone excess, consideration should be given to the known efficacy and safety data specific to pregnant women for each therapeutic option. In healthy women, pituitary gland size increases during pregnancy. Since some pituitary adenomas also enlarge during pregnancy, there is a risk of visual impairment, especially in women with macroadenomas or tumours near the optic chiasm. Pituitary apoplexy represents a rare acute complication of adenomas requiring surveillance, with surgical intervention needed in some cases. This guideline describes the choice and timing of diagnostic tests and treatments from the pre-conception stage until after delivery, taking into account adenoma size, location and endocrine activity. In most cases, pregnant women with pituitary adenomas should be managed by a multidisciplinary team in a centre specialised in the treatment of such tumours.

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Type 4 Renal Tubular Acidosis (RTA) Induced by Spironolactone Use in Secondary Adrenal Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.329 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A162-A163

Author(s):

Claudia Villatoro Santos ◽

Lisa De Rose ◽

Nikoletta Proudan

Keyword(s):

Adrenal Insufficiency ◽

Renal Tubular Acidosis ◽

The Elderly ◽

Altered Mental Status ◽

Secondary Adrenal Insufficiency ◽

Acth Stimulation ◽

Primary Adrenal Insufficiency ◽

Inhaled Steroids ◽

Baseline Cortisol ◽

Renal Tubular

Abstract Type 4 RTA is caused by either decreased aldosterone production or resistance. Primary adrenal insufficiency results in decreased aldosterone whereas spironolactone can cause aldosterone resistance1. We present a case of spironolactone-induced type 4 RTA in a patient with suspected primary adrenal insufficiency. A 70-year-old female with liver cirrhosis on spironolactone and chronic bronchitis on inhaled steroids (ICS) presented for altered mental status. Laboratories showed hyponatremia 131 mmol/L (135–145 mmol/L) and hyperammonemia 113 µmol/L (11–51 µmol/L). She was successfully treated with oral lactulose for hepatic encephalopathy. However, on day 3, she developed worsening hyponatremia (126 mmol/L) and hyperkalemia 5.8 mmol/L (3.5–5.4 mmol/L). Spironolactone was discontinued, and hyperkalemia improved after medical treatment. Nonetheless, hyperkalemia recurred with worsening hyponatremia (125 mmol/L), hypoglycemia (57 mg/dL), and mild non-anion gap metabolic acidosis without other signs or symptoms of adrenal insufficiency. On day 5, her morning cortisol was 1.5 µg/dL (5–20 µg/dL), with ACTH 11 pg/mL (6–70 pg/mL). Her hyperkalemia persisted (6.3–6.8 mmol/L), and she was started on oral patiromer. Due to suspected adrenal insufficiency, she received dexamethasone 10 mg daily, and endocrinology was consulted. On day 7, an ACTH stimulation test (250 µg IV) showed a baseline ACTH <3 pg/mL, baseline cortisol 0.7 µg/dL (3–15 µg/dL), cortisol 30 minutes 9.9 µg/dL, and 60 minutes 12.2 µg/dL, consistent with incomplete response attributed to the supraphysiologic dexamethasone versus chronic ICS. On day 8, endocrinology discontinued dexamethasone and enoxaparin, and started hydrocortisone 10 mg orally in AM and 5 mg in PM. Aldosterone (measured at day 6) was 7.2 ng/dL (<= 31.0 ng/dL), renin activity 3.1 ng/mL/hr (0.5–4.0 ng/mL/hr), and aldosterone/renin ratio 2.3 (<= 25) consistent with hyporeninemic hypoaldosteronism since aldosterone and renin were inappropriately normal for the hyperkalemia. Repeat cosyntropin test on day 11 showed low ACTH (3 pg/mL), low baseline cortisol 1.1 µg/dL, cortisol 30 minutes 7.9 µg/dL, and 60 minutes 11.2 µg/dL, consistent with secondary adrenal insufficiency, ascribed to chronic ICS. Potassium level normalized seven days after spironolactone discontinuation, related to its approximate duration of action1. The patient was discharged with hydrocortisone 10 mg daily, and spironolactone was permanently discontinued. Spironolactone use can result in type 4 RTA due to aldosterone resistance and mimic mineralocorticoid deficits characteristic of primary adrenal insufficiency. 1. O’Connell JE, Colledge NR. Type IV renal tubular acidosis and spironolactone therapy in the elderly. Postgrad Med J. 1993;69(817):887–889.

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Successful Multimodal Treatment of a TSH-Secreting Pituitary Adenoma (TSH-oma)

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1247 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A611-A612

Author(s):

Donna Lee ◽

Lakshmi Mahali ◽

Vafa Tabatabaie

Keyword(s):

Adrenal Insufficiency ◽

Pituitary Adenomas ◽

Somatostatin Analogs ◽

Surgical Techniques ◽

Mass Effect ◽

Symptomatic Improvement ◽

Therapeutic Management ◽

Secondary Adrenal Insufficiency ◽

Α Subunit ◽

Laboratory Results

Abstract Background: TSH-omas are rare tumors accounting for 0.5-2% of all pituitary adenomas. Due to their indolent nature, most TSH-omas are diagnosed at the stage of invasive macroadenomas. Over the past several decades, the management of TSH-omas has evolved substantially. While surgery remains first-line therapy, somatostatin analogs have emerged as important therapeutic agents as a result of their effectiveness in normalizing thyroid hormone levels in ~95% of patients with severe hyperthyroidism and reducing TSH-oma size in ~50% of patients. Clinical Case: A 52-year-old woman with a history of multinodular goiter was incidentally found to have a 2.2 x 1.8 x 2.1 cm pituitary macroadenoma with suprasellar extension, mass effect on the optic chiasm, and left cavernous sinus involvement when she presented with chest pain, palpitations, headache, and left-sided numbness and weakness. Laboratory results showed high FT4/T4/T3 with inappropriately high TSH, elevated α-subunit, and low cortisol with low-normal ACTH highly suggestive of TSH-oma with concurrent secondary adrenal insufficiency. An ophthalmology exam revealed a left superior temporal defect. The patient was treated with atenolol, prednisone, and octreotide two weeks before surgery with symptomatic improvement and near-normalization of FT4. Following an uncomplicated transsphenoidal resection, FT4 normalized within one week. At her one-month follow-up, both TSH and FT4 were normal, and her secondary adrenal insufficiency had resolved. Her visual field defect also recovered. Laboratory Results: TSH 5.35 (normal range 0.40-4.60 μU/mL), FT4 3.0 (0.8-1.7 ng/dL), T4 18.1 (5.0-12.0 μg/dL), T3 235 (80-200 ng/dL), ACTH 10 (6-50 pg/mL), cortisol 4.5 (5.0-25.0 μg/dL), α-subunit 8.0 (0.1-1.5 ng/mL); after 2 weeks on SQ octreotide 50mg q12h: TSH 1.93 (0.30-4.20 μU/mL), FT4 1.7 (0.6-1.5 ng/dL); 1 month post-op: TSH 1.53 (0.30-4.20 μU/mL), FT4 0.8 (0.6-1.5 ng/dL), ACTH 12 (7.2-63 pg/mL), cortisol 6.9 (4.0-20.0 μg/dL) Conclusion: Since the first reported case of TSH-oma in 1960, the diagnostic and therapeutic management of these rare pituitary adenomas have evolved due to the emergence of ultrasensitive TSH assays, advanced imaging and surgical techniques, and somatostatin analogs. However, to this day, most TSH-omas are still diagnosed at the stage of invasive macroadenomas, when successful surgical resection becomes more difficult. Hence, up to two-thirds of patients may require adjuvant therapy with medication or radiation. As evidenced in our patient, who achieved a near-euthyroid state within just two weeks of starting low dose octreotide, somatostatin analogs are highly effective in controlling hyperthyroidism and have solidified their place in the therapeutic management of TSH-omas. This case highlights the success of a multimodal approach to the treatment of TSH-omas.

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SUN-311 Adrenal Reserve Testing with the Glucagon Stimulation Test (GST) and Cosyntropin Stimulation Test (CST) in Deployed Veterans with Mild Traumatic Brain Injury

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.604 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Rama Priyanka Nagireddi ◽

Htet Htet Win ◽

Sarah Wagstaff ◽

Moira Neal ◽

Kathryn Friedman ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Adrenal Insufficiency ◽

Mild Traumatic Brain Injury ◽

Stimulation Test ◽

Pituitary Hormone ◽

Secondary Adrenal Insufficiency ◽

Glucagon Stimulation Test ◽

Cortisol Levels ◽

Cosyntropin Stimulation Test

Abstract Introduction: Mild Traumatic Brain Injury (mTBI) is associated with anterior pituitary hormone dysfunction. The potential long-term effect of this injury on pituitary function in Veterans is not clear. We reviewed the utility of the fixed dose Glucagon Stimulation Test (GST) compared with the high dose Cosyntropin Stimulation test (CST) for hypothalamic-pituitary-adrenal (HPA) reserve over time in these patients with mTBI. Methods: We present an interim report of our 4-year longitudinal prospective pilot study of pituitary function in Veterans diagnosed with mTBI. Of the 34 mTBI Veterans enrolled, we have tested 28 of them (4 female, 24 male; age and BMI, 31.5±7.0 years and 30.4±6.2, mean±SD, respectively) for baseline pituitary hormone levels and cortisol response to the CST. In 22 subjects growth hormone and cortisol responses to GST were tested at baseline (Year 0). Follow-up testing was done for 18 mTBI subjects in Year 1, 13 subjects in Year 2, 10 subjects in Year 3 and 5 subjects in Year 4. The same baseline data were obtained for 14 age-, sex-, deployment- and BMI-matched control subjects without mTBI (2 female,12 male; age and BMI 34.4±6.8 years and 30.5±4.9, mean±SD, respectively). Cortisol cutoffs of <18 mcg/dL with the CST and <9.0 mcg/dL with the GST were used for the diagnosis of adrenal insufficiency. Results: Secondary adrenal insufficiency (AI), likely partial, was identified during this study on 6 occasions: 3/22 subjects at Year 0, 1/18 at Year 1, 0/13 at Year 2, 1/10 at Year 3 and 1/5 at Year 4. Two baseline subjects with AI reverted to normal in Years 1-3, one relapsed in Year 4 and a third had no further testing. Correlations of the cortisol levels from GST vs the 60-minute cortisol from CST were significant at Year 0 (n=22, r=0.553, p=0.008) and at Year 1 (n=18, r=0.802, p<0.0001). Due to decreased numbers, there were no significant correlations at Years 2 through 4. Similar correlations were obtained using the 30-minute CST values. However, the CST cortisol value predicted the low GST value in only 2/6 subjects. The mean GST cortisol levels and 60-minute CST cortisol levels for subjects at each year were not significantly different over Years 0 through 4 based on ANOVA analyses (CST: F=1.519, p= 0.206; GST: F= 0.796, p=0.532). Conclusions: Secondary adrenal insufficiency, likely partial, related to mTBI was detected by GST on 6 occasions (twice in one patient) over 4 years of observation. GST can provide useful information about HPA axis reserve, and appears to be more reliable than CST. Identification of potential secondary adrenal insufficiency using the GST in Veterans with mTBI can provide a beneficial combined test for these patients when other testing is not feasible.

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