Enlargement Of Hands Research Articles

9234 A Case of Gigantism Due to An AIP Gene Mutation: Implications for Genetic Counseling and Preimplantation Genetic Diagnosis

Abstract Disclosure: M. Serebro: None. M. Yacobi Bach: None. N. Even Zohar: None. A. Reches: None. Y. Greenman: None. From the age of 17 the patient experienced accelerated growth, facial changes, and enlargement of hands and feet. Despite having a sister already diagnosed with acromegaly, the patient did not undergo endocrine evaluation until the age of 25, when he was diagnosed with gigantism. Magnetic resonance imaging (MRI) revealed the presence of a macroadenoma with suprasellar extension reaching the optic chiasm. The patient underwent transsphenoidal surgery and excision of a sparsely granulated somatotroph adenoma that was Pit1 positive and exhibited weak immunostaining for growth hormone (GH). Insulin-like growth factor 1 (IGF1) levels normalized after surgery, and a fasting GH level was 0.6 ng/ml. Given the family history and the early onset of the disease, genetic counseling was recommended. Genetic testing revealed a heterozygote likely pathogenic variant in the AIP gene (c.713G>A). This finding prompted the recommendation for genetic testing of all first-degree relatives. The patient and his wife, who desired to have children, were referred to obstetrics and gynecology for pregestational diagnosis. Family segregation testing indicated that the patient's mother also carried the same AIP variant. Preimplantation genetic diagnosis (PGD) was conducted, revealing that 11 out of 20 embryos were carriers of the AIP variant. The non-carrier embryos were selected for implantation, and pregnancy was achieved. Efforts to inform first-degree relatives about the importance of genetic testing were undertaken, and one sister was tested and found to be healthy. Other siblings have not yet been tested. The patient's mother, identified as an AIP variant carrier, underwent endocrine laboratory tests that showed GH, IGF1, and prolactin levels within the normal range. Brain MRI did not reveal a pituitary lesion.This case highlights the significance of genetic counseling and testing in patients with familial endocrine disorders, the potential implications of a molecular diagnosis of a pathogenic AIP variant, and the challenges faced in reproductive decision-making for affected individuals and their families. Presentation: 6/3/2024

SAT-249 Polyarticular Osteoarthritis: A Disabling Manifestation of Acromegaly

BackgroundAcromegaly is a slow-onset rare endocrinopathy that is characterized by chronic overproduction of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Excess GH and IGF-1 levels lead to insulin resistance, which is implicated in most of the complications associated with acromegaly. We present a case of acromegaly, wherein the patient presented with worsening polyarthralgia and decreasing mobility. As the patient was undergoing workup for rapidly progressing osteoarthritis, the internist became suspicious of patient’s changing physical appearance.CaseA 53-year-old man with medical history of diabetes mellitus and hypertension was referred to endocrine clinic on account of high IGF-1 levels, 909 ng/ml (normal: 37-245 ng/ml). He was seeking medical attention because of rapidly progressing polyarthralgia and stiffness for the last two years. His symptoms were intensifying despite use of non-steroidal anti-inflammatory drugs and intra-articular steroid injections. Imaging revealed severe degenerative changes and narrowing of joint space in bilateral hip, knee and glenohumeral joints. Internist observed that the patient was exhibiting stigmata of acromegaly such as enlargement of hands and feet, prognathism and dental space widening. Patient reported headaches, blurry vision, sleep apnea, dysphagia and right ear exostosis. Colonoscopy revealed hyperplastic polyps.Repeat IGF- 1 levels were 910 ng/ml (Normal: 37-245 ng/ml). Oral glucose tolerance test showed failure of suppression of GH. Serial GH levels were 4.50, 5.08, 6.74, 5.81 and 5.21 ng/ml (Normal: 0.01- 0.97 ng/ml).Tests for other endocrinopathies revealed the following results: serum prolactin 4 ng/ml (Normal <18 ng/ml), serum cortisol 7.9 ug/dl (Normal: 6-27 ug/dl), 24 hour urine cortisol 23mcg/24 hours (Normal: 3.5-45 mcg/24 hours), serum TSH 2.25 uIU/ml (Normal: 0.34- 3 uIU/ml), serum T4 level 0.7 ng/dl (Normal: 0.6-1.6 ng/dl) and serum T3 level 144.9ng/dl (Normal: 87-178 ng/dl). Serum total and free testosterone levels were 111 ng/dl (Normal: 240-950 ng/dl) and 3.89 ng/dl (Normal: 4.06-15.6 ng/dl) respectively and were suggestive of hypogonadism.MRI Brain showed 12x10x8mm pituitary adenoma. He was referred for transsphenoidal surgery for resection of pituitary adenoma.ConclusionPolyarticular osteoarthritis is an early manifestation of acromegaly. Systemic diseases associated with acromegaly are the primary reason for which most patients seek medical attention. It is important to look for coexisting endocrinopathies whenever the diagnosis of acromegaly is established, since mass effect of pituitary adenoma can wreak havoc on the endocrine system of the body. High index of suspicion, early diagnosis and prompt treatment are the key to reverse some but not all comorbid conditions associated with acromegaly.

Case of acromegalic myopathy and arthropathy long after trans‐sphenoidal surgery

AbstractAcromegaly patients usually show impaired vision, the enlargement of hands and feet, heart failure, and diabetes and rarely show myopathy (weakness and muscle pain) and arthropathy (joint pain). Here, we report an acromegaly patient who showed progressive myopathy and arthropathy long after a Hardy operation. The symptoms of myopathy and arthropathy occurred under normal GH and high IGF‐1 levels, but these symptoms improved when the IGF‐1 level was normalized by a treatment of octreotide with an increased dose of 30–40 mg. Thus, strict and immediate control of IGH‐1 may be pivotally important to prevent and treat acromegalic myopathy and arthropathy.

Enlarged hands and feet - Not always acromegaly

Pachydermoperiostosis maybe mistaken for acromegaly as it can present with progressive enlargement of hands and feet. We describe a 32 year old male with enlargement of hands and feet and extensive keloid formation. Family history was positive for similar complaints. X ray imaging showed normal heel pad thickness with acroosteolysis and subperiosteal new bone formation in hands and feet. IGF-1 was normal and glucose suppressed GH values were normal.

Case report: Acromegaly or end-stage renal disease?

Introduction: A 41 year old female patient with end-state renal disease (ESRD) caused by interstitial nephritis came to our outpatient clinic. A renal transplantation was planned soon. During the routine examination before transplantation, a slightly elevated IGF-I level was found. We were to clarify whether she had acromegaly. Medical history: Body size unchanged since puberty, shoe size increased 1 size during the last 10 years. No enlargement of hands, no sweating, no head pain, regular menses. Physical examination: 1.82m, 72kg, blood pressure 145/80mmHg, heart rate 59/min, lean fingers and tongue not swollen, thyroid slightly enlarged. Evaluation: At first visit: IGF-I 340µg/l (Immulite®, age- and gender-specific normal values 97–263µg/l), hGH 7.1µg/l (&lt;5µg/l), IGF-BP3 5870µg/l (3500–6600µg/l), creatinine and urea elevated. Re-evaluation 5 weeks later: An oral glucose tolerance test was performed. No suppression of GH was seen (basal 3.4µg/l, nadir 1.7µg/l), but a paradoxical increase (11µg/l) after 60min. Corresponding IGF-I 273µg/l (97–263µg/l) was elevated again (IGF-BP3 5410µg/l (3500–6600µg/l)). We initiated a MRI of the sella region, which showed no pituitary adenoma. Blood samples were sent to another laboratory (DSL, Heidelberg) for reassessment in a different assay. The results showed elevated IGF-I and IGF-BP3 levels in both samples (717 and 677µg/l (101–303µg/l), 8117 and 8474µg/l (2080–4310µg/l)). Follow up: Renal transplantation was carried out 3 weeks later. 21 months later, a blood sample was taken again. Now GH (0.2µg/l), IGF-I (251µg/l) and IGF-BP3 levels (4140µg/l) were within the normal range.

GONADOTROPH ADENOMA WITH MARKEDLY ELEVATED TESTOSTERONE LEVELS.

Purpose of Study To present a case of a gonadotroph adenoma with markedly elevated testosterone levels. A review of relevant literature is also included. Methods A 61-year-old African American male was referred for evaluation of persistent headaches. Symptoms initially started 5 months earlier with bifrontal, pounding headaches and right temporal hemianopia. He admitted to decreased sexual activity and overall energy level, as well as increased facial hair growth. He denied any galactorrhea or enlargement of hands or feet. Examination was significant for mildly enlarged testes but no testicular masses. MRI revealed a pituitary macroadenoma measuring 2.7 × 2.2 cm, with extension into the right cavernous sinus and elevation of the optic chiasm. Results Laboratory workup to assess for secretory capacity was initiated. Prolactin was 24 ng/mL (2.1-17.7 ng/mL), LH 15.7 mIU/mL (1.5-9.3 mIU/mL), FSH 102.9 mIU/mL (1.4-18.1 mIU/mL), and total testosterone 2,270 ng/dL (241-827 ng/dl). He subsequently underwent successful transsphenoidal resection of the adenoma. Immunoperoxidase staining of the tissue was strongly positive for LH and weakly positive for FSH. Eighteen days postoperatively, laboratory results showed LH 1.6 mIU/mL, FSH 18.1 mIU/mL, and total testosterone 58 ng/dL. Conclusions Gonadotroph adenomas may produce supranormal concentrations of intact LH, which can rarely cause a supranormal testosterone concentration. The endocrinologist should be aware of this entity to facilitate diagnosis in the future.

P0202 PROGRESSIVE FAMILIAL INTRA HEPATIC CHOLESTASIS (PFIC) WITH LOW GAMMA GLUTAMYL- TRANS PEPTIDASE (GGT) LEVELS IN TUNISIAN INFANTS ABOUT 32 CASES

Introduction: Progressive familial intra hepatic cholestasis has been distinguished from other forms of cholestatic liver disease in childhood by clinical findings, clinical-laboratory observations and morphologic studies in biopsy. The aim of the study is to investigate the clinical aspects of PFIC with low GGT in Tunisian patients. Methods: 32 cholestatic infants from 16 unrelated families were retrospectively reviewed. The diagnosis was performed by combination of clinical (pruritus) biological (cholestasis with normal or low level of GGT and normal level of chlesterol), histological features, familial history and high level of serum primary bile acids (done for 40%). Results: The age at presentation ranged from the neonatal period to 12 months. Consanguinity was found in 80%. The constant features were pruritus and hepatomegalia. Short stature found in 58% of infants. Twelve infants have lichenification and enlargement of hands and feet. The cytolysis was important in 45% (> 10N). The histological study was performed for all the patients and showed cirrhosis with inflammatory features and cholestasis. For infants have vesicular lithiasis (12.5%). Response to AUCD treatment was in 55%. Eleven infants (34%) developed portal features respectively at age 5 months and 7 years old. Nine infants (28%) were dead at age from 5 months to 15 years old. Six of them had important cytolysis (>10N) at the presentation. The age of survival infants was ranged from 3.5 to 21.8 years. Conclusion: The prognosis of infants with PFIC can be ameliorated by the development of hepatic transplantation not yet available in our country. Only molecular study if performed will be able to distinguish different form of PFIC 1 and 2.