Preface

Comprehending endocrine disorders requires a combination of basic knowledge on molecular biology and genetics as well as a good grasp of the clinical aspects. Given the recent advances in these fields, an overview of the latest trends and developments affecting endocrinology is provided.

As one of the most up to date publications on this specialist field, this book is the result of a collaboration between a number of leading researchers and practitioners in the field who are recognized for their work over the years in the field of endocrinology. The book provides and indepth analysis across a range of topics focused on hormonal and metabolic disorders.

The book aims to provide a basic as well as advanced recent trends in endocrine disorders in addition to an analytical focus on those topics less well-studied. Readers will find a large spectrum of endocrinopathise from thyroid carcinogenesis and pituitary adenomas to adrenal tumors and metabolic bone disease. Emphasis has also been focused on more specific issues not yet fully elucidated (e.g. the molecular pathways involved in thyrotropin beta gene regulation or monogenic phosphate balance disorders).

We hope that the scope of this book is not only to answer questions but mainly to stimulate new questions.In sharing the knowledge, of the eminent scientists and clinicians in this book with a broad spectrum of readers,it will spark new interest in the expanding spectrum of endocrine disorders.

The book is organized into the following sections:

**I. INTRODUCTION TO ENDOCRINOLOGY** including the chapter « The power of an evolutionary perspective in studies of endocrinology» by Dr. Zhang Yaping et al.; a review focused on recent advances in the understanding of the evolution of hormone signalling pathways.

**II. PITUITARY ADENOMAS** including the following chapters:

 «The Genetics of Pituitary Adenomas» by Dr. Fedele Monica et al.; a review on pituitary adenomas covering a wide spectrum from pituitary tumorigenesis to sporadic and familiar pituitary adenomas.

	- «Acromegaly and Gigantism» by Dr. Akin Fulya et al.; authors attempt to provide data concerning the history, epidemiology, etiology, pathophysiology, clinical features, diagnosis and treatment of acromegaly.

Preface XI

 «Adrenal incidentaloma and adrenocortical carcinoma» by Dr. Sasaki Shigekazu et al.; an up-to-date review focused on the molecular mechanisms of negative

«Adrenal Cortex Tumors and Hyperplasias» by Prof. Pignatelli Duarte; a

«Autoimmunity to steroid-producing cells» by Dr. Falorni Alberto et al; a review

 «Exrretion of Steroid Hormones in Rodent: An overview on species differences for new biomedical animal research models» by Dr. Busso Juan Manuel et al.; a review analyzing the routes of gonadal and adrenocortical steroid excretion based

 «New trends in Calcium and Phosphorus metabolism. Hypoparathyroidism» by Dr. Puig-Domingo Manuel et al.; a review specialized on the regulation of the metabolism of calcium and phosphorus and their integrated pathways to

«Monogenic phosphate balance disorders» by Dr. Raeder et al.; a review focused

 «Pseudohypoparathyroidism in Children» Dr. Nwosu Benjamin; a review focused on pseudohypoparathyroidism's diagnosis , treatment and management in

«Retinoids and Bone» by Prof. Lerner Ulf et al.; a review on the impact of Vitamin

We have learned that there is an endocrinology of elation and despair, a chemistry of mystical insight, and, in relation to the autonomic nervous system, a meteorology and even... an astro-physics of changing moods. - Aldous (Leonard) Huxley, *Literature and* 

**Prof. Dr. Evanthia Diamanti-Kandarakis** 

Greece

University of Athens Medical School, Sotiria Hospital, Athens,

A on bone remodeling, skeletal mass and osteoclast differentiation.

thorough revision on adrenal cortex tumors and hyperplasias.

on data derived from wild , laboratory and farm rodents.

maintain their levels within physiological limits.

on phosphate disorders- diagnosis and treatment.

children.

*Science (1963)* 

**V. METABOLIC BONE DISEASE** including the following chapters:

**IV. ADRENAL GLANDS** including the following chapters:

regulation of the TSH beta gene by T3.

of the genetic basis of adrenal autoimmunity.

 «Effects of Growth hormone (GH) over-expression on signaling cascades involved in promotion of cell proliferation and survival» by Dr. González Lorena et al.; authors analyze the effects of long term exposure to growth hormone (GH) at the molecular level in the liver.

## **III. THE THYROID GLAND** including the following chapters:


## **IV. ADRENAL GLANDS** including the following chapters:

X Preface

 «Acromegaly and Gigantism» by Dr. Akin Fulya et al.; authors attempt to provide data concerning the history, epidemiology, etiology, pathophysiology, clinical

 «Effects of Growth hormone (GH) over-expression on signaling cascades involved in promotion of cell proliferation and survival» by Dr. González Lorena et al.; authors analyze the effects of long term exposure to growth hormone (GH) at the

 «Negative regulation of the thyrotropin beta gene by T3» by Dr. Sasaki Shigekazu et al.; an up-to-date review focused on the molecular mechanisms of negative

 «Clinical management of thyroid nodules in the areas of various iodine supply» by Prof. Słowińska-Klencka Dorota et al.; a review is focused on the clinical management of thyroid nodules in areas of different iodine status (high, sufficient

 «Clinical Workup of Nodular and Mass Lesions of the Endocrine Organs» by Dr. Lin Xiaoqi et al.; a review focused on the application of FNA biopsy for thyroid

 «Molecular biology of thyroid cancer» by Prof. Viglietto Giuseppe et al.; a revision on thyroid tumorigenesis covering a wide literature spectrum from epidemiology and risk factors of thyroid cancer to the mechanisms and molecular pathways that

 «Diagnosis and differential diagnosis of medullary thyroid cancer» by Dr. Faggiano Antongiulio et al.; a review focused on the pathogenesis, diagnosis and

 «Molecular Diagnostics in Treatment of Medullary Thyroid Carcinoma» by Prof. Pützer Brigitte et al.; a review focused on new perspectives in the molecular

 «Medullary thyroid carcinoma associated with RET mutations located in exon» by Dr. Peppa Melpomeni et al.; a chapter focused on the genetic analysis of the RET protooncogene -apart from the known somatic mutations in exons 10, 11, 13-16,

 «Status for congenital hypothyroidism at advanced ages» by Dr. Ari Yuca Sevil; a review focused on the multi-systemic abnormalities provoked by congenital

diagnostic approach of patients with medullary thyroid cancer.

authors analyze another " non classical" exon mutation in exon 8.

features, diagnosis and treatment of acromegaly.

**III. THE THYROID GLAND** including the following chapters:

underlie onset and progression of these neoplasms.

therapeutic approach of medullary thyroid cancer.

molecular level in the liver.

regulation of the TSH beta gene by T3.

or inadequate iodine supply).

and parathyroid lessions.

hypothyroidism later in life.


**V. METABOLIC BONE DISEASE** including the following chapters:


We have learned that there is an endocrinology of elation and despair, a chemistry of mystical insight, and, in relation to the autonomic nervous system, a meteorology and even... an astro-physics of changing moods. - Aldous (Leonard) Huxley, *Literature and Science (1963)* 

> **Prof. Dr. Evanthia Diamanti-Kandarakis**  University of Athens Medical School, Sotiria Hospital, Athens, Greece

**Part 1** 

**Introduction to Endocrinology** 

**Part 1** 

**Introduction to Endocrinology** 

**1** 

*1,3China 2Canada* 

**The Power of an Evolutionary Perspective in** 

*1State Key Laboratory of Genetic Resource and Evolution, Kunming Institute of Zoology,* 

Much of our understanding of the molecular basis of endocrinology has been the product of highly productive studies that have focused on specific molecules (e.g., hormones) and their specific immediate interacting partners. However, biomolecules are not isolated particles, but instead they are elements of highly integrated interaction networks, and specific interactions among them drive virtually all cellular functions and underlie phenotypic complexity and diversity. Many hormones, and their specific receptors and other interacting proteins, are known to be evolutionarily related, which raises intriguing questions

Our previous studies have illustrated that biochemical entities are developmentally and evolutionarily fluid, with capabilities to be altered both in composition and behavior. Gene birth and death are widespread phenomena in genome evolution and accounts for the great diversity of gene families involved in endocrinology. While concordance of evolutionary histories both in pattern and process of hormones, receptors and interacting proteins might be expected for integrated systems, studies have shown that the evolutionary history of receptors need not mirror that of their ligands. Simultaneous emergence, or loss, of multiple interacting partners by multiple gene duplication or gene loss is unlikely in evolution. Gene duplication is essential in the development of complex endocrinology. It is creative in producing elements that allow evolutionary tinkering and thus plays a major role in gene co-option (i.e., recruitment for novel functions) facilitating the evolution of greater biological complexity. Alternatively, if an interacting partner is lost, the retained partner may either be subsequently lost or, more interestingly, serve as raw material in evolution and become recruited into a new interaction yielding a new function. Thus, a stepwise process of elaboration through mutation and optimization ensues, adapting genes (and their encoded

Here we review several recent advances in our understanding of the evolution of hormone signalling pathways that illustrate the power of an evolutionary perspective. Among our

concerning how specificity originated within these systems.

proteins) into the physiology of an organism.

**1. Introduction** 

*2Department of Laboratory Medicine and Pathobiology and Banting and Best Diabetes* 

*3Laboratory for Conservation and Utilization of Bioresource, Yunnan University* 

**Studies of Endocrinology** 

*Chinese Academy of Sciences* 

*Centre, University of Toronto* 

Jing He1, David M. Irwin1,2 and Ya-Ping Zhang1,3
