Endocrinology Flashcards
Maternal hypoparathyroidism can present in the following ways except:
A. Maternal hypotonia
B. Muscle cramps or paresthesia
C. Fetal growth restriction
D. Fetal skeletal fractures
A.
Maternal hypoparathyroidism can present with the signs of maternal hypocalcemia and resultant fetal or neonatal hyperparathyroidism. Hypoparathyroidism most often occurs as a consequence prior thyroid or parathyroid surgery but can be associated with DiGeorge syndrome, pseudohypoparathyrodisim, magnesium depletion, idiopathic hypoparathyroidism, or as a consequence of genetics reflecting activating mutations in calcium-sensing receptors. The clinical manifestations are those of hypocalcemia including tetany (not hypotonia, Answer A) elicited as the Chvostek test or Trousseau test and associated with any of the aforementioned maternal symptoms (B, E). Neonatal hyperparathyroidism is a consequence of maternal hypocalcemia and can result in fetal bone demineralization leading to growth restriction (C) or skeletal fractures (D)
Maternal levels of leptin are elevated in all of the following conditions except:
A. Obesity
B. Fetal growth restriction
C. Normal pregnancy
D. Preeclampsia
E. Gestational diabetes
B.
Maternal leptin serum levels steadily increase during the first and second trimesters and peak in late second or early third trimester. These high levels are maintained throughout the remainder of gestation and decline drastically postpartum. This suggests a functional importance of leptin during pregnancy. Given the contributions from adipose tissue and placenta, maternal serum leptin levels are even higher throughout pregnancy in pregnant overweight/obese (BMI >26 kg/m 2 ) in comparison to non-overweight pregnant women (BMI <26 kg/m 2 ). This increase is presumably due to increased adiposity as the source of higher leptin secretion since placental leptin expression has been shown to be comparable in both groups. In the context of pregnancy complications, leptin has been readily studied in women suffering from gestational diabetes mellitus because of the known dysregulated glycemic control, the common association with maternal obesity and fetal macrosomia. In these pregnancies an increase in placental leptin levels and no change in total placental OB–R levels have been reported whereas the soluble form OB–Re has been found to be elevated. Preeclampsia (PE) is a severe complication of pregnancy characterized by multisystemic dysfunction and endothelial damage leading to hypertension, altered adipokines and heightened inflammation. In such pregnancies, maternal circulating leptin and placental leptin gene expression and protein levels are elevated when compared to healthy controls. In pregnancies complicated by FGR, multiple studies have reported varied placental leptin expression patterns such that it is difficult to draw conclusions regarding the possible role of leptin in this pathology. All these studies characterized leptin mRNA and protein expression in SGA and AGA fetuses at or near term and the majority of placental tissues were collected by caesarean section. However, results remain contradictory which could partly be explained by the potential biases unaccounted for (e.g. failing to match for relevant variables).
Role of leptin in pregnancy: consequences of maternal obesity. Tessier DR, Ferraro ZM, Gruslin A. Placenta, 2013 Mar;34(3):205-11.
. Which of the following accurately describes the relation of circulating adiponectin levels in pregnancy?
A. Large for gestational age babies are associated with the largest drop in adiponectin levels
B. Small for gestational age babies are associated with moderate drop in levels
C. Large for gestational age babies are associated with the largest rise in levels
D. Small for gestational age babies are associated with the largest rise in levels
E. Both small and large for gestational age babies are associated with sharper rises in levels in the third trimester
A.
Adiponectin decreases most from early to late pregnancy in mothers who give birth to LGA offspring, and this decrease is an independent predictor of birth weight. Circulating adiponectin levels are lower in mothers where the offspring have the highest AC late in pregnancy. The decrease in systemic adiponectin levels in mothers who gave birth to LGA offspring accompanied a placental decrease in mRNA levels of the adiponectin receptor ADIPOR2. Maternal adiponectin may be an important predictor of fetal growth and birth weight, independent of BMI, gestational weight gain, and insulin resistance.
. All of the following are true about ghrelin in pregnancy except?
A. Increased ghrelin levels are associated with feelings of hunger
B. Ghrelin levels are decreased in obesity
C. Levels continue to increase throughout pregnancy
D. The placenta produces ghrelin
E. Ghrelin signal growth hormone release
B.
It is well documented that energy requirements are increased during pregnancy. These increased demands can be met through metabolic adaptations and increased dietary intakes. The significant decrease in circulating maternal ghrelin during the third trimester of normal pregnancy is hypothesized to be a response to the marked changes in maternal weight and energy expenditure. Therefore, it is possible that the decreased plasma ghrelin concentrations during normal pregnancy may represent a physiological adaptation to the positive energy balance during pregnancy. It has been recently demonstrated that plasma ghrelin concentration was decreased in obesity and that plasma ghrelin concentration was negatively correlated with body mass index. However, it is unclear whether the decreased plasma ghrelin concentration is involved in energy balance during pregnancy. Further investigations are needed to clarify the possible involvement of ghrelin in energy homeostasis during pregnancy. Another interesting finding is that ghrelin concentrations in umbilical artery blood are higher than those in maternal blood normal pregnant women, suggesting that the fetal-placental unit may contribute to its production. Furthermore, it was recently demonstrated that ghrelin mRNA and ghrelin peptides are present in the human and in rat placentae. These findings thus also suggests that ghrelin may have some role not only in maternal circulation but also in fetal-placental circulation. In conclusion, although it still remains to be elucidated whether ghrelin has biological actions other than growth hormone secretion and food intake, our results suggest for the first time that ghrelin may have some important role in cardiovascular control during normal pregnancy and in pathophysiological conditions in pregnancy, such as hypertensive disorders of pregnancy.
A patient with recurrent renal calculi is noted to have an elevated calcium level, confirmed on repeat with ionized calcium. The level of parathyroid hormone is low. Which of the following is most likely to be a cause of her hypercalcemia?
A. Lithium use
B. Excessive vitamin d intake
C. Diuretic use
D. Vitamin d deficiency
E. Hyperparathyroidism
B.
Hypercalcemia can be due to many causes including parathyroid mediated causes and non-parathyroid mediated causes. The low PTH in this example suggests non-parathyroid mediated causes which include vitamin D intoxication, hypercalcemia of malignancy (diagnosed with elevated PTHrp) and chronic granulomatous disorders. The next step in the workup of this patient would be the measurement of PTHrP, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D to help determine the underlying etiology. Medication use including thiazide diuretics and lithium both cause hypercalcemia through the mediation of PTH.
Lafferty FW. Differential diagnosis of hypercalcemia. J Bone Miner Res. 1001;6 Suppl 2:S51. 2) Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR. Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009;94(2):351.
A patient presents with recurrent renal calculi and is found to have an elevated ionized calcium level with an elevated PTH. She goes on to deliver without complications but is diagnosed once more with renal stones in the postpartum period. You recommend the following management:
A. Hydration
B. Tamsulosin
C. Evaluation for parathyroidectomy
D. Initiation of bisphosphonates
E. Lithotripsy
C.
Though hydration or Tamsulosin may be helpful adjuncts for management of her renal stones, her symptomatic primary hyperparathyroidism warrants surgical management with parathyroidectomy as definitive management. Parathyroidectomy decreases the risk of kidney stones, improves bone mineral density, and may decrease fracture risk long-term. Indications for surgery in asymptomatic individuals include serum calcium 1 mg/dL or more above the upper limit of normal, skeletal indications including T-score <-2.5 on bone mineral density testing, prior asymptomatic vertebral fracture, asymptomatic nephrolithiasis, or age less than 50 years old.
Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561.
Proposed physiologic roles of leptin in pregnancy include all EXCEPT:
A. Regulation of growth and development of the conceptus
B. Sexual differentiation in early embryonic life
C. fetal/placental angiogenesis
D. Embryonic hematopoiesis
E. Hormone biosynthesis with the maternal-feto-placental unit
B.
Leptin is a polypeptide hormone that aids in the regulation of body weight and energy homeostasis and is linked to a variety of reproductive processes in both animals and humans. Thus, leptin may help regulate ovarian development and steroidogenesis and serve as either a primary signal initiating puberty or as a permissive regulator of sexual maturation. However it has not been demonstrated to have an impact on embryonic sexual differentiation, therefore this is the correct answer to the question. Perhaps significantly, peripheral leptin concentrations, adjusted for adiposity, are dramatically higher in females than in males throughout life. During primate pregnancy, maternal levels that arise from adipose stores and perhaps the placenta increase with advancing gestational age. Proposed physiological roles for leptin in pregnancy include the regulation of conceptus growth and development, fetal/placental angiogenesis, embryonic hematopoiesis, and hormone biosynthesis within the maternal-fetoplacental unit. The specific localization of both leptin and its receptor in the syncytiotrophoblast implies autocrine and/or paracrine relationships in this endocrinologically active tissue. Interactions of leptin with mechanisms regulating pre-eclampsia and maternal diabetes have also been suggested. Collectively, therefore, reports suggest that a better understanding of the regulation of leptin and its role(s) throughout gestation may eventually impact those causes of human perinatal morbidity and mortality that are exacerbated by intrauterine growth retardation, macrosomia, placental insufficiency, or prematurity.
Biology of Reproduction, Volume 63, Issue 5, 1 November 2000, Pages 1219–1228,https://doi.org/10.1095/biolre…
All of the following are true regarding adiponectin in pregnancy except:
A. Is secreted by hepatocytes in response to periods of starvation
B. Is down-regulated in patients with GDM
C. Decreased maternal levels are associated with fetal macrosomia
D. Levels are associated with pancreatic beta cell function
E. Subclinical inflammation has been associated with lower levels of adiponectin
A.
Adiponectin, an anti-inflammatory agent secreted by adipose tissue have been shown to be down-regulated in GDM affected females. It is not secreted by hepatocytes in response to periods of starvation, therefore that answer should be selected. In a study by Tsai et al., they have demonstrated that decreased maternal adiponectin levels and insulin sensitivity may increase risk of macrosomic baby in females with GDM. Another study by Retnakaran and Associates have demonstrated a strong correlation between adiponectin levels and pancreatic beta cell function during late pregnancy. Subclinical inflammation has been associated with lower levels of adiponectin. A case control study by Ategbo et al., has shown that the levels of adiponectin are decreased in women with GDM as compared to their healthy controls and similar results were observed by Meller et al.. Lower levels of adiponectin has also been associated with beta cell dysfunction and also linked to future development of type 2 diabetes mellitus. Based on these findings, adiponectin could be an associated factor for causing GDM. However, more clarity is required in this aspect, with the help of large-scale comparative studies.
Siddiqui S, et al., Role of immunological markers in gestational diabetes mellitus-a brief review, Diabetes & Metabolic Syndrome: Clinical Research & Reviews (2018)
- Compared to maternal serum levels of ionized calcium fetal serum levels of ionized calcium levels are what
A. Higher than maternal serum levels
B. Equal to maternal serum levels
C. Less than maternal serum levels
A.
Calcium is an essential nutrient for the developing fetus, and ionized calcium levels are higher in fetal than in maternal blood. Higher fetal calcium levels are due to a syncytiotrophoblast basal membrane ATP-dependent Ca 2+ transport system that exhibits high affinity for calcium. Calcium transport across the placenta is increased by the calcium-dependent regulatory protein calmodulin, regulated by 1,25 dihydroxycholecalciferol, calcitonin, parathyroid hormone–related protein, and parathyroid hormone.
Gabbe (editor). Obstetrics: Normal and problem pregnancies, 7th edition. Chapter 1, 2-25.
Which of the following will make the fetus of a mother with hyperthyroidism to be at high risk for developing fetal/neonatal graves hyperthyroidism?
A. Anti-thyroglobulin antibody
B. Anti-microsomal antibody
C. Thyroid peroxidase antibody
D. Thyroid stimulating hormone receptor antibody
D.
The thyrotropin binding inhibitory immunoglobulin, TBII assay is used to check for Thyroid Stimulating Hormone Receptor Antibody (TRAb). It is recommended to check for this antibody around 24-28 weeks in order to predict if infant is at high risk for developing fetal/neonatal Graves hyperthyroidism. The risk is highest when maternal value is 3-5x the upper limit of normal. Ultrasound screening for goiter is an important approach to be considered.
References: Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice 8th Edition
by Robert Resnik MD (Author), Charles J. Lockwood MD MHCM (Author), Thomas Moore MD (Author),
Proposed physiologic roles of leptin in pregnancy include all EXCEPT:
A. Regulation of growth and development of the conceptus
B. Sexual differentiation in early embryonic life
C. fetal/placental angiogenesis
D. Embryonic hematopoiesis
E. Hormone biosynthesis with the maternal-feto-placental unit
B.
Leptin is a polypeptide hormone that aids in the regulation of body weight and energy homeostasis and is linked to a variety of reproductive processes in both animals and humans. Thus, leptin may help regulate ovarian development and steroidogenesis and serve as either a primary signal initiating puberty or as a permissive regulator of sexual maturation. However it has not been demonstrated to have an impact on embryonic sexual differentiation, therefore this is the correct answer to the question. Perhaps significantly, peripheral leptin concentrations, adjusted for adiposity, are dramatically higher in females than in males throughout life. During primate pregnancy, maternal levels that arise from adipose stores and perhaps the placenta increase with advancing gestational age. Proposed physiological roles for leptin in pregnancy include the regulation of conceptus growth and development, fetal/placental angiogenesis, embryonic hematopoiesis, and hormone biosynthesis within the maternal-fetoplacental unit. The specific localization of both leptin and its receptor in the syncytiotrophoblast implies autocrine and/or paracrine relationships in this endocrinologically active tissue. Interactions of leptin with mechanisms regulating pre-eclampsia and maternal diabetes have also been suggested. Collectively, therefore, reports suggest that a better understanding of the regulation of leptin and its role(s) throughout gestation may eventually impact those causes of human perinatal morbidity and mortality that are exacerbated by intrauterine growth retardation, macrosomia, placental insufficiency, or prematurity.
Biology of Reproduction, Volume 63, Issue 5, 1 November 2000, Pages 1219–1228,https://doi.org/10.1095/biolre…
All of the following are true regarding adiponectin in pregnancy except:
A. Is secreted by hepatocytes in response to periods of starvation
B. Is down-regulated in patients with GDM
C. Decreased maternal levels are associated with fetal macrosomia
D. Levels are associated with pancreatic beta cell function
E. Subclinical inflammation has been associated with lower levels of adiponectin
A.
Adiponectin, an anti-inflammatory agent secreted by adipose tissue have been shown to be down-regulated in GDM affected females. It is not secreted by hepatocytes in response to periods of starvation, therefore that answer should be selected. In a study by Tsai et al., they have demonstrated that decreased maternal adiponectin levels and insulin sensitivity may increase risk of macrosomic baby in females with GDM. Another study by Retnakaran and Associates have demonstrated a strong correlation between adiponectin levels and pancreatic beta cell function during late pregnancy. Subclinical inflammation has been associated with lower levels of adiponectin. A case control study by Ategbo et al., has shown that the levels of adiponectin are decreased in women with GDM as compared to their healthy controls and similar results were observed by Meller et al.. Lower levels of adiponectin has also been associated with beta cell dysfunction and also linked to future development of type 2 diabetes mellitus. Based on these findings, adiponectin could be an associated factor for causing GDM. However, more clarity is required in this aspect, with the help of large-scale comparative studies.
Siddiqui S, et al., Role of immunological markers in gestational diabetes mellitus-a brief review, Diabetes & Metabolic Syndrome: Clinical Research & Reviews (2018)
Compared to maternal serum levels of ionized calcium fetal serum levels of ionized calcium levels are what
A. Higher than maternal serum levels
B. Equal to maternal serum levels
C. Less than maternal serum levels
A.
Calcium is an essential nutrient for the developing fetus, and ionized calcium levels are higher in fetal than in maternal blood. Higher fetal calcium levels are due to a syncytiotrophoblast basal membrane ATP-dependent Ca 2+ transport system that exhibits high affinity for calcium. Calcium transport across the placenta is increased by the calcium-dependent regulatory protein calmodulin, regulated by 1,25 dihydroxycholecalciferol, calcitonin, parathyroid hormone–related protein, and parathyroid hormone.
Gabbe (editor). Obstetrics: Normal and problem pregnancies, 7th edition. Chapter 1, 2-25.
Which of the following is the most accurate statement about the role and physiologic variations of adiponectin? ***
A. Maternal exercise decreases levels, adiponectin decreases insulin sensitivity, high levels early in pregnancy are a predictor for GDM
B. Maternal levels of adiponectin are stable throughout pregnancy, but placental productions varies widely, high placental levels are associated with an increased risk of GDM
C. Maternal levels are inversely correlated with BMI, adiponectin increases insulin sensitivity, low levels early in pregnancy are a predictor for GDM
D. Maternal exercise increases levels, adiponectin increases insulin sensitivity, low levels early in pregnancy are a predictor for GDM
E. Maternal levels are proportional with BMI, adiponectin decreases insulin sensitivity, high levels early in pregnancy are a predictor for GDM
C.
Adiponectin is a master regulatory protein in metabolic homeostasis, which has both insulin-sensitizing and anti-inflammatory properties. Plasma adiponectin levels decrease in a variety of situations associated with loss of insulin sensitivity, such as obesity, metabolic syndrome, diabetes, and various cancers. Its role during pregnancy has been examined because of the necessity for decreasing maternal insulin sensitivity to provide nutrients and ensure growth of feto-placental tissues. Circulating adpN levels are decreased during the third trimester when maternal insulin sensitivity is reduced compared with the first and second trimesters.1
In women who developed GDM at 28 weeks of pregnancy, adiponectin concentrations were lower (p < 0.05). Adiponectin remained lower at the time of GDM diagnosis (p < 0.05), while the other adipokines were similar between groups at each timepoint.2
In all, 591 were randomized to the intervention and 605 women to control groups. Women in the intervention group reported modestly higher levels of physical activity compared with control women, and fewer women in the intervention group reported no physical activity during pregnancy. Fasting glucose, lipid, insulin, leptin, and adiponectin levels were similar in the two groups, as was insulin sensitivity and the incidence of gestational diabetes.
Which of the following is excreted from mammary tissue to regulate calcium during lactation?
A. 1,25-dihydroxy vitamin d
B. Parathyroid hormone related peptide
C. Calcitonin
D. 25-hydroxy vitamin D
B.
The serum calcium level is tightly regulated by parathyroid hormone (PTH) and vitamin D. PTH regulates calcium metabolism by resorbing bone and stimulating the formation of vitamin D. PTHrp is homologous with PTH and shares a common receptor.
Answer D is the form of vitamin D synthesized from the skin or absorbed from dietary sources (also known as 25-hydroxycholecalciferol or vitamin D3) that goes on to be hydroxylated in the liver and kidney to be physiologically active.
Answer A is the physiologically active form of vitamin D (also known as 1,25-dihydroxycholecalciferol, calcitriol, or vitamin D2).
During lactation, the mammary tissue releases PTHrp with a goal of mobilization of calcium for transfer to the breastfeeding neonate and use in the neonatal skeleton. PTHrp serves to decrease PTH excretion from the parathyroid gland, decrease urinary calcium excretion, increase hydroxylation of vitamin D in the kidney, and increase intestinal calcium reabsorption.
Calcitonin levels are high in lactation and are thought to regulate the rate of skeletal resorption during this time.
